Affinage

ISL1

Insulin gene enhancer protein ISL-1 · UniProt P61371

Length
349 aa
Mass
39.0 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ISL1 is a LIM-homeodomain transcription factor that acts as a master regulator of progenitor specification and differentiation across cardiac, endocrine, and neural lineages (PMID:1691825, PMID:31024170). It was first identified as an insulin gene enhancer-binding factor defining a new class of proteins combining a homeodomain with tandem N-terminal Cys-His (LIM) domains (PMID:1691825); these LIM domains can autoinhibit homeodomain DNA binding in vitro, an effect relieved by truncation (PMID:7901000). In cardiac progenitor cells ISL1 functions as a pioneer factor, binding compacted chromatin and cooperating with the Brg1-Baf60c SWI/SNF complex to open cardiac lineage loci and establish epigenetic memory of cardiomyocyte fate (PMID:31024170), and it recruits the H3K27me3 demethylase JMJD3 to enhancers of cardiac targets such as Myocd and Mef2c to drive their demethylation and activation (PMID:27105846). Its cardiac expression is positioned within signaling circuits: beta-catenin directly activates the Isl1 promoter to control cardiovascular progenitor renewal (PMID:17519333, PMID:18371348), while Nkx2-5 directly represses an Isl1 enhancer, tuning nodal versus ventricular myocyte identity (PMID:23093675, PMID:25524439). ISL1 directly binds and regulates lineage-defining target enhancers in multiple tissues, including the FGF10 second-heart-field enhancer (PMID:22303449), the sinoatrial-node program (L-type calcium channel subunits, Ank2, Tbx3) (PMID:26193633), pancreatic beta-cell maturation genes (Pdx1, Slc2a2, MafA) (PMID:19502415, PMID:25028525), the alpha-cell determinant Arx (PMID:21388963), and retinal ganglion cell genes acting in an obligate complex with Pou4f2/Brn3b (PMID:18434421, PMID:25775587). It executes these programs through combinatorial partnerships with cofactors and complexes including SSBP3/Ldb1 in beta cells (PMID:26495868), LHX3/LHX4 at the Slit2 enhancer in motor neurons (PMID:27819291), GATA3 in neuroblastoma (PMID:30867811), CREB on the somatostatin promoter (PMID:1352885), and the repressor CIP (PMID:22343712). Consistent with these roles, conditional Isl1 loss disrupts cardiac, pancreatic, enteroendocrine, pituitary, sympathetic, auditory, retinal, kidney, and limb development (PMID:17607356, PMID:19502415, PMID:25214396, PMID:32453714, PMID:29445148, PMID:36074819, PMID:18434421, PMID:23641053, PMID:22438573).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Established the molecular identity of ISL1, defining it as a transcription factor that binds the insulin enhancer and founds the LIM-homeodomain class.

    Evidence cDNA isolation, DNA-binding assay, and sequence analysis identifying a homeodomain and a novel LIM domain

    PMID:1691825

    Open questions at the time
    • Did not establish in vivo regulatory targets
    • Function of the LIM domains undefined at this stage
  2. 1993 High

    Defined an intramolecular regulatory mechanism by showing the LIM domains autoinhibit homeodomain DNA binding, framing ISL1 activity as conformationally gated.

    Evidence In vitro DNA binding with bacterially expressed protein, LIM truncation/denaturation, and in vivo reporter assay

    PMID:7901000

    Open questions at the time
    • Physiological trigger relieving autoinhibition unidentified
    • Conflicting context where full-length ISL1 binds DNA (e.g. proglucagon)
  3. 1992 High

    Showed ISL1 acts combinatorially with other transcription factors, synergizing with CREB to activate islet hormone gene expression rather than acting alone.

    Evidence DNA-binding and reporter transfection assays on the somatostatin promoter in islet cells

    PMID:1352885

    Open questions at the time
    • Direct physical CREB-ISL1 interaction not mapped
    • Generality across promoters unknown
  4. 2000 High

    Revealed a non-genomic regulatory role in which ISL1 LIM domains sequester nuclear receptors, blocking estrogen receptor dimerization and DNA binding.

    Evidence Reciprocal co-IP, in vitro interaction, EMSA dimerization assay, and reporter assays

    PMID:11043578

    Open questions at the time
    • Physiological context of ISL1-ER crosstalk unclear
    • Single-lab finding
  5. 2005 Medium

    Connected ISL1 to cytoplasmic signaling by showing it engages JAK1/STAT3 to drive STAT3 phosphorylation and neural progenitor proliferation.

    Evidence Co-IP, in vitro kinase assay, and chick neural tube electroporation reporter/proliferation assays

    PMID:15659653

    Open questions at the time
    • Mechanism of JAK1 activation by a transcription factor unresolved
    • Not independently replicated
  6. 2007 High

    Placed ISL1 within Wnt/beta-catenin control of cardiovascular progenitors, showing beta-catenin directly drives the Isl1 promoter and governs progenitor renewal versus differentiation.

    Evidence Conditional KO, ChIP on the Isl1 promoter, and in vivo beta-catenin gain/loss with FGF readouts

    PMID:17519333 PMID:17607356 PMID:18371348

    Open questions at the time
    • Direct ISL1 targets downstream not all defined here
    • Quantitative thresholds for renewal vs differentiation unknown
  7. 2008 High

    Defined ISL1 as a node in lineage-specific gene regulatory networks across retina and sensory neurons, acting in complex with Brn3b/Pou4f2 and required for subtype specification.

    Evidence Conditional KO, ChIP, transactivation assays, double-KO epistasis, and microarray profiling

    PMID:18434421 PMID:18460603 PMID:18849985

    Open questions at the time
    • Full direct target set not enumerated
    • Cofactor selectivity across neuron classes unclear
  8. 2009 High

    Established ISL1 as a Notch/beta-catenin-balanced regulator of cardiac progenitor expansion and a determinant of endocrine pancreas maturation, identifying MafA as a direct target.

    Evidence Conditional KO, ES cell differentiation, pathway epistasis, and pancreatic morphometry

    PMID:19502415 PMID:19620969

    Open questions at the time
    • Direct vs indirect Notch input on Isl1 not fully resolved
    • Genome-wide beta-cell targets not yet mapped
  9. 2011 High

    Demonstrated direct ISL1 occupancy of lineage and proliferation gene enhancers (Arx, c-Myc, CyclinD1) and a role in axon outgrowth via dpysl3, extending its direct-target repertoire.

    Evidence ChIP, reporter/mutagenesis, knockdown/overexpression, cell-cycle analysis, and zebrafish mutant/morpholino epistasis

    PMID:21108318 PMID:21388963 PMID:21829621 PMID:21937598

    Open questions at the time
    • Cofactor requirements at these enhancers undefined
    • Cell-type specificity of c-Myc/CyclinD1 regulation unclear
  10. 2012 High

    Mapped ISL1 to a defined cardiac enhancer (FGF10 first intron) co-bound with Nkx2-5 and identified the CIP repressor, refining how ISL1 output is combinatorially set in the heart.

    Evidence ChIP, EMSA, transgenic reporter assays, yeast two-hybrid, and co-IP

    PMID:22303449 PMID:22343712 PMID:22438573 PMID:23093675

    Open questions at the time
    • Stoichiometry of ISL1/GATA4/TBX20 enhancer complexes unknown
    • CIP regulation in vivo not fully tested
  11. 2014 High

    Provided genome-wide direct-target evidence in beta cells (Pdx1, Slc2a2) and characterized the Ldb1-Isl1-SSBP3 complex and ISL1 functions in enteroendocrine specification.

    Evidence Inducible beta-cell KO, ChIP-seq, RNA-seq, mass spectrometry, co-IP, and intestinal conditional KO with physiology

    PMID:24643061 PMID:25028525 PMID:25214396 PMID:26495868

    Open questions at the time
    • Direct vs network-level effects on secretion genes not fully separated
    • SSBP3 complex composition across tissues unknown
  12. 2015 High

    Defined ISL1 as essential for sinoatrial pacemaker identity with direct ion-channel gene targets and showed Nkx2-5 repression of Isl1 sets nodal vs ventricular fate.

    Evidence Multiple SAN-specific KO lines, ChIP and RNA-seq on FACS-purified SAN cells, ESC/Xenopus gain-of-function, and electrophysiology

    PMID:25524439 PMID:25775587 PMID:26193633

    Open questions at the time
    • Direct vs indirect contribution to one-third of SAN genes not parsed
    • Mechanism of fate switching at single-cell level unclear
  13. 2016 High

    Identified the epigenetic mechanism by which ISL1 activates cardiac genes — recruitment of the H3K27me3 demethylase JMJD3 — and extended combinatorial control to motor-neuron Slit2.

    Evidence Co-IP, ChIP-seq, H3K27me3 ChIP, JMJD3 knockdown phenocopy, and Slit2 enhancer reporter/KO

    PMID:27105846 PMID:27819291

    Open questions at the time
    • How ISL1 modulates JMJD3 catalytic activity mechanistically unknown
    • Generality of JMJD3 recruitment beyond heart untested
  14. 2018 Medium

    Established ISL1 control of cardiomyocyte chamber identity (anti-atrial, antagonized by RA/MEIS2/NR2F1) and its broad role in sympathetic neuron development with direct targets.

    Evidence hESC depletion with RNA-seq/pathway epistasis and sympathetic ganglia RNA-seq/ChIP-seq from two KO lines

    PMID:29337667 PMID:29445148

    Open questions at the time
    • Direct ISL1 binding at NR2F1/MEIS2 not demonstrated
    • Single-system chamber-identity data
  15. 2019 High

    Defined ISL1 as a bona fide pioneer factor that opens compacted cardiac chromatin via the Brg1-Baf60c SWI/SNF complex, and extended its roles to foregut separation.

    Evidence Isl1 hypomorph, ISL1 ChIP-seq, ATAC-seq, RNA-seq, co-IP, and Xenopus/mouse foregut KO with lineage tracing

    PMID:31024170 PMID:31813798

    Open questions at the time
    • Determinants of ISL1 pioneer site selection on nucleosomes unknown
    • Order of SWI/SNF vs JMJD3 recruitment unresolved
  16. 2024 Medium

    Revealed regulated nuclear import of ISL1 (EphrinB2-CDK5) as a signaling-controlled switch driving VEGFR3 transcription and cardiac lymphangiogenesis, and oncogenic ISL1 networks in neuroblastoma/lymphoma.

    Evidence EphrinB2 KO/overexpression, CDK5 assay, nuclear translocation, VEGFR3 ChIP, plus neuroblastoma co-IP/ChIP-seq and AURKA pathway epistasis

    PMID:25070240 PMID:30867811 PMID:34131100 PMID:39557830

    Open questions at the time
    • Direct CDK5 phosphosites on ISL1 not mapped
    • Causality of ISL1 in tumor maintenance vs initiation unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ISL1 selects its tissue-specific pioneer sites and integrates distinct cofactor partnerships (SWI/SNF, JMJD3, Ldb1/SSBP3, POU/LHX, GATA3) to produce divergent lineage outputs remains unresolved.
  • No structural model of ISL1 on nucleosomal or enhancer DNA with cofactors
  • Rules governing context-specific LIM-domain autoinhibition relief unknown
  • No timeline evidence linking ISL1 to a defined human Mendelian disease via causative mutation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0042393 histone binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3
Partners
CREBGATA3JMJD3LDB1LHX3POU4F2SSBP3STAT3
Complex memberships
Brg1-Baf60c SWI/SNF complex (with ISL1)ISL1-LHX3/LHX4 complexISL1-Pou4f2/Brn3b complexLdb1-Isl1-SSBP3 complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 ISL1 (Isl-1) was identified as a transcription factor that binds to the rat insulin I gene enhancer. It contains both a homeodomain (most similar to C. elegans mec-3 and lin-11) and a novel Cys-His (LIM) domain, defining a new class of LIM-homeodomain proteins. cDNA isolation, DNA-binding assay, sequence analysis Nature High 1691825
1993 The LIM domains of ISL1 inhibit DNA binding by the associated homeodomain in vitro; this inhibition can be released by denaturation/renaturation or truncation of the LIM domains, and LIM domains from a chimeric protein can also inhibit DNA binding by the Ubx homeodomain. A similar inhibitory effect was observed in vivo with reporter constructs. In vitro DNA binding assay with bacterially expressed protein, LIM domain truncation/denaturation, in vivo reporter assay The EMBO journal High 7901000
1992 ISL1 (Isl-1) and CREB synergize on the somatostatin promoter to stimulate high-level expression in pancreatic islet cells; ISL1 binds a second promoter element distinct from the CRE site required for somatostatin expression. DNA-binding assay, functional transcription assay (reporter transfection), pancreatic islet cell line (Tu6) Proceedings of the National Academy of Sciences of the United States of America High 1352885
1995 ISL1 (isl-1) functions as a positive transcriptional regulator of the proglucagon gene through binding to Gb/Gc promoter elements; the LIM domains do not prevent DNA binding by full-length isl-1 in this context (in contrast to other reports), and isl-1 antisense cells showed loss of Gb/Gc-mediated activation. DNA binding assay (EMSA with isl-1 antisera), reporter gene transfection, isl-1 antisense cell lines The Journal of biological chemistry Medium 7759514
1996 ISL1 activates rat amylin (IAPP) gene transcription by binding AT-rich TAAT motifs in the amylin promoter via its homeodomain; EMSA with isl-1 antisera confirmed isl-1 complex formation with hAMY sequences in islet cell nuclear extracts. Mutation of TAAT motifs markedly reduced transcriptional activity. EMSA, reporter gene transfection, site-directed mutagenesis, isl-1 antisense cell lines Molecular endocrinology (Baltimore, Md.) High 8833653
2000 ISL1 directly interacts in vivo and in vitro with the estrogen receptor (ER), as well as with various other nuclear receptors; the interaction is mediated at least in part by the ligand-binding domain of ER and is strengthened by estradiol. As a consequence, ISL1 prevents ER dimerization and inhibits ER DNA binding activity via its N-terminal LIM domains; ISL1 specifically inhibits ER-driven transcriptional activation in some promoter contexts, while ER can serve as a coactivator for ISL1 in others. Co-immunoprecipitation (in vivo), in vitro interaction assay, EMSA (ER dimerization), reporter gene assay, dual immunohistochemistry Molecular endocrinology (Baltimore, Md.) High 11043578
2005 ISL1 physically interacts with JAK1 and STAT3 (but not STAT1 or STAT5) and triggers tyrosine phosphorylation of JAK1, thereby elevating phospho-STAT3 DNA binding and target gene expression. ISL1 and STAT3 co-electroporation in chick neural tube activated a STAT3-reporter; co-transfection promoted motor neuron cell proliferation. Co-immunoprecipitation, in vitro kinase assay, reporter gene assay (electroporation in chick embryo), cell proliferation assay Molecular biology of the cell Medium 15659653
2007 Beta-catenin directly regulates the Isl1 promoter in cardiovascular progenitors; ablation of beta-catenin in Isl1-expressing progenitors disrupts cardiogenesis and reduces expression of downstream genes including Tbx2, Tbx3, Wnt11, Shh, and Pitx2. Conditional knockout (Cre/loxP), chromatin immunoprecipitation (ChIP) on Isl1 promoter, reporter assay Proceedings of the National Academy of Sciences of the United States of America High 17519333
2007 Wnt/beta-catenin signaling controls the renewal and differentiation of Isl1+ cardiovascular progenitors; in vivo activation of beta-catenin in Isl1+ progenitors leads to their massive accumulation and inhibition of differentiation, while beta-catenin deletion in Isl1+ precursors reduces OFT myocyte mitosis rate. In vivo conditional activation/deletion of beta-catenin in Isl1+ cells (Cre/loxP), ES cell-derived progenitor reconstitution, Wnt3a feeder layer expansion assay Cell stem cell High 18371348
2007 ISL1 is required for expansion of Isl1-positive anterior heart field progenitors; Wnt/beta-catenin loss in these cells reduces Isl1-positive progenitor number and FGF signaling, while Wnt gain of function expands progenitors with concomitant increase in FGF3, FGF10, FGF16, and FGF20 expression, revealing a Wnt-FGF signaling axis downstream of Isl1 progenitors. Conditional knockout and gain-of-function mouse genetics (Cre/loxP), gene expression analysis The Journal of clinical investigation High 17607356
2008 ISL1 and BRN3B form a complex that directly binds and synergistically activates a common set of RGC-specific target genes; whole-retina ChIP and in vitro transactivation assays confirmed co-occupancy of shared targets. Retina-specific deletion of Isl1 causes apoptosis of most RGCs and axon guidance defects; Isl1/Brn3b double-null retinas show near-complete RGC loss. Conditional knockout (Cre/loxP), ChIP, in vitro transactivation assay, genetic epistasis (double KO) Development (Cambridge, England) High 18434421
2008 ISL1 is required for the transition from sensory neurogenesis to subtype specification; conditional knockout of Isl1 in sensory ganglia results in loss of nociceptive markers TrkA and Runx1, near-absence of cutaneous innervation, ectopic expression of CNS transcription factors, and prolonged expression of early developmental regulators. Conditional knockout (Cre/loxP), microarray gene expression analysis, immunostaining Nature neuroscience High 18849985
2008 ISL1 functions downstream of Math5 in RGC development, defining a branch of the RGC gene regulatory network distinct from but overlapping with the Pou4f2 branch; Isl1 is required for sustained expression of Pou4f2, indicating ISL1 positively regulates Pou4f2 after Math5 levels diminish. Conditional knockout (Cre/loxP), microarray analysis, genetic epistasis Proceedings of the National Academy of Sciences of the United States of America High 18460603
2009 Notch1 positively, and beta-catenin negatively, regulate expression of Isl1 in cardiac progenitor cells (CPCs). Disruption of Isl1 in CPCs results in their expansion in vivo and in an ES cell system; furthermore, Isl1 is required for CPC differentiation into cardiomyocyte and smooth muscle cells but not endothelial cells. Conditional knockout (Cre/loxP), ES cell differentiation assay, epistasis analysis Nature cell biology High 19620969
2009 Isl1 is required for maturation, proliferation, and survival of endocrine pancreas cells during the secondary transition; Isl1-deficient endocrine precursors fail to mature into functional islet cells, and MafA was identified as a direct transcriptional target of Isl1 in pancreatic beta cells. Conditional knockout (Cre/loxP, from E13.5), gene expression analysis, morphometry Diabetes High 19502415
2011 ISL1 directly regulates transcription of the Arx gene in pancreatic alpha cells by binding to two conserved noncoding regulatory regions (Re1 and Re2) within the Arx locus, as demonstrated by ChIP and cell-based reporter/knockdown/overexpression assays. ChIP, reporter assay, site-directed mutagenesis, knockdown, overexpression, Isl1 conditional KO mouse The Journal of biological chemistry High 21388963
2011 ISL1 promotes pancreatic islet cell proliferation by directly binding and activating c-Myc and CyclinD1 promoters; knockdown of ISL1 increases apoptosis and G1 arrest. ChIP, reporter assay, knockdown/overexpression, cell cycle analysis PloS one Medium 21829621
2011 ISL1 is required in zebrafish Rohon-Beard neurons for selective peripheral axon outgrowth by maintaining expression of dpysl3 (CRMP4); morpholino knockdown of dpysl3 inhibits peripheral axon outgrowth, and the effect is enhanced by semaphorin 3d knockdown. Zebrafish mutant (lullaby/isl1), morpholino knockdown (dpysl3, sema3d), gene expression analysis Developmental dynamics Medium 21108318
2012 ISL1 directly binds the FGF10 first intron enhancer in the second heart field in vivo (demonstrated by ChIP and EMSA); ISL1-mediated transcription from this FGF10 element is enhanced by co-expression of GATA4 and TBX20. ChIP, EMSA, reporter assay (transgenic mice), co-transfection PloS one High 22303449
2012 ISL1 directly binds conserved sites overlapping with Nkx2-5 binding sites in the Fgf10 first intron cardiac enhancer; ChIP shows ISL1 binding in vivo in anterior second heart field, and Nkx2-5 represses Isl1 (and consequently Fgf10) in differentiating myocardium. ChIP, transgenic reporter assay, genetic gain/loss-of-function Proceedings of the National Academy of Sciences of the United States of America High 23093675
2012 CIP (Cardiac Isl1-Interacting Protein) directly interacts with ISL1 via mapped protein domains; CIP represses Isl1 transcriptional activity toward MEF2C, and overexpression of CIP represses agonist-induced cardiomyocyte hypertrophy. CIP was identified by yeast two-hybrid screening. Yeast two-hybrid screen, co-immunoprecipitation, reporter assay (Isl1/MEF2C), overexpression (cardiomyocyte hypertrophy assay), in situ hybridization Circulation research Medium 22343712
2014 Isl1 and Pou4f2 form a physical complex in vitro and in vivo; domain mapping by GST pulldown and co-immunoprecipitation identified the interacting domains; both factors contribute quantitatively to expression of common target genes in developing RGCs, and each factor can interact with other POU and LIM-homeodomain family members respectively. GST pulldown, co-immunoprecipitation, EMSA, luciferase assay, in situ hybridization, RNA-seq PloS one High 24643061
2014 Postnatal beta-cell-specific deletion of Isl1 impairs insulin secretion and glucose tolerance without reducing beta-cell mass. ChIP-seq identified Isl1 directly occupying regulatory elements of Pdx1 and Slc2a2 (GLUT2), confirming these as direct targets in beta cells. Tamoxifen-inducible conditional KO (Pdx1-CreER), ChIP-seq, RNA-seq, luciferase reporter assay, physiological glucose tolerance testing Diabetes High 25028525
2015 ISL1 is essential for survival, proliferation, and function of sinoatrial node (SAN) pacemaker cells throughout development. ChIP assays with anti-ISL1 antibodies on FACS-purified SAN cells demonstrated that ISL1 directly binds genomic regions of L-type calcium channel subunits, Ank2, and Tbx3, and regulates approximately one-third of SAN-specific genes. Multiple conditional KO mouse lines (SAN-specific), RNA-seq on FACS-purified SAN cells, ChIP on FACS-purified SAN cells The Journal of clinical investigation High 26193633
2015 Nkx2-5 directly represses Isl1 transcriptional activity by binding to an Isl1 enhancer; overexpression of Isl1 in ESCs and Xenopus shifts cardiomyocyte subtype identity toward nodal/pacemaker (Hcn4+) at the expense of ventricular fate, with increased beating frequency. ESC differentiation, ChIP (Nkx2-5 binding to Isl1 enhancer), conditional KO (Nkx2-5 in Isl1+ cells), Xenopus gain-of-function, optical action potential imaging, pharmacology Stem cells (Dayton, Ohio) High 25524439
2015 Ectopic co-expression of Pou4f2 and Isl1 in the Atoh7-null retina is sufficient to specify functional RGC fate, demonstrating that Pou4f2 and Isl1 compose a minimally sufficient regulatory core for RGC fate downstream of Atoh7. Binary knockin-transgenic ectopic expression in Atoh7-null retina, gene expression analysis, electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 25775587
2016 ISL1 physically interacts with the H3K27me3 demethylase JMJD3; ISL1 recruits JMJD3 to enhancers of cardiac target genes (Myocd, Mef2c) and modulates its demethylase activity, promoting H3K27me3 demethylation. Conditional depletion of JMJD3 phenocopies ISL1 depletion in cardiac progenitor differentiation. Co-immunoprecipitation, ChIP-seq, H3K27me3 ChIP, conditional knockdown/KO, ESC cardiac differentiation assay Nucleic acids research High 27105846
2018 ISL1 depletion delays cardiac differentiation in hESCs and respecifies nascent cardiomyocytes from ventricular to atrial identity; this anti-atrial function of ISL1 is antagonized by retinoic acid signaling through MEIS2, and ISL1 competes with the retinoic acid pathway for prospective cardiomyocyte fate converging on the atrial specifier NR2F1. hESC ISL1 depletion (CRISPR/siRNA), RNA-seq, pathway analysis, epistasis with RA/MEIS2/NR2F1 eLife Medium 29337667
2019 ISL1 acts as a pioneer transcription factor in cardiac progenitor cells by binding to compacted chromatin and working in concert with the Brg1-Baf60c-based SWI/SNF complex to open chromatin at cardiac lineage-specific genes (both progenitor and cardiomyocyte structural genes), establishing epigenetic memory of cardiomyocyte fate. Isl1 hypomorphic mice show congenital heart defects correlated with impaired chromatin opening. Isl1 hypomorphic mouse, ISL1 ChIP-seq, ATAC-seq, RNA-seq, co-IP (ISL1-Brg1-Baf60c), genome-wide chromatin profiling Cell research High 31024170
2019 ISL1 regulates Nkx2.1 transcription in midline epithelial cells (MECs) of the anterior foregut to orchestrate trachea-esophageal separation; lineage tracing shows ISL1+ MECs contribute to both tracheal and esophageal epithelium, and Isl1 conditional deletion disrupts foregut morphogenesis. Xenopus and mouse conditional KO, lineage tracing, gene expression analysis Developmental cell High 31813798
2015 SSBP3 interacts with Ldb1 and ISL1 in beta-cell lines, mouse, and human islets; SSBP3 knockdown reduces expression of known Ldb1-Isl1 target genes (MafA, Glp1r) and SSBP3 occupies known Ldb1-Isl1 target promoters, establishing SSBP3 as a critical component of Ldb1-Isl1 regulatory complexes in beta cells. Cross-linked immunoprecipitation/mass spectrometry, co-immunoprecipitation, ChIP, siRNA knockdown, RT-PCR, immunostaining Molecular endocrinology (Baltimore, Md.) High 26495868
2013 Leptin suppresses Isl1 expression in pancreatic islets via STAT3 (downstream of leptin receptor OBRb); ISL1 acts as a direct downstream target of STAT3 in mediating leptin's effect on insulin secretion. This effect is lost in leptin receptor-defective db/db mice and in Isl1-inducible knockout mice. In vivo and in vitro leptin treatment, Isl1 inducible KO mouse (db/db model), gene expression analysis, physiological insulin secretion measurement The Journal of biological chemistry Medium 23504315
2016 ISL1-LHX3 and ISL1-LHX4 complexes bind to the Slit2 enhancer and drive endogenous Slit2 expression in somatic motor and branchiomotor neurons, respectively; Isl1 conditional knockout in cranial branchiomotor neurons disrupts their migration and peripheral axon pathfinding, with near-absent Slit2 expression. Isl1 conditional KO mouse, reporter assay (Slit2 enhancer), ChIP-seq data analysis, in situ hybridization Scientific reports Medium 27819291
2018 ISL1 is required for multiple aspects of sympathetic nervous system development including neuronal fate determination, differentiation, repression of glial differentiation, proliferation (via cell cycle gene regulation), axon growth, and maintenance of noradrenergic/repression of cholinergic differentiation. RNA-seq and ISL1 ChIP-seq on sympathetic ganglia identified direct ISL1 target genes, including several neuroblastoma-associated genes. Isl1 hypomorphic and neural crest-specific KO mouse lines, RNA-seq, ChIP-seq on sympathetic ganglia Cell death & disease High 29445148
2019 ISL1 plays an essential role in neuroblastoma regulatory networks; ISL1 physically interacts with GATA3 and co-occupies binding regions genome-wide to synergistically regulate oncogenic pathways. ISL1 directly regulates LMO1, LIN28B, and cell cycle genes while repressing differentiation genes including RA receptors. RNA-seq (ISL1 KD in SH-SY5Y), ISL1 ChIP-seq, co-immunoprecipitation (ISL1-GATA3), in vitro and in vivo knockdown Theranostics Medium 30867811
2014 Intestinal epithelial-specific deletion of Isl1 causes loss of GLP-1, GIP, CCK, and somatostatin-expressing enteroendocrine cells and an increase in serotonin-producing cells, with impaired incretin effect and lipid malabsorption, establishing ISL1 as required for specification of multiple enteroendocrine cell subtypes. Conditional KO (Villin-Cre/loxP), hormone cell immunostaining, oral glucose tolerance test American journal of physiology. Gastrointestinal and liver physiology High 25214396
2012 Isl1 is required for establishing the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory pathway; conditional inactivation of Isl1 in the hindlimb-forming region (Hoxb6Cre) causes loss of posterior hindlimb structures, downregulation of Hand2, and severe impairment of Shh expression specifically in the hindlimb. Conditional KO (Hoxb6Cre/loxP), gene expression analysis (Hand2, Shh), limb morphology Development (Cambridge, England) High 22438573
2011 ISL1 is required for nuclear accumulation of beta-catenin and hence activation of the beta-catenin pathway in the hindlimb-forming lateral plate mesoderm; ISL1 and beta-catenin regulate Fgf10 expression and the Fgf10-Fgf8 feedback loop during hindlimb initiation. Conditional KO of Isl1 and beta-catenin (lateral plate mesoderm-specific), nuclear/cytoplasmic fractionation (beta-catenin localization), gene expression analysis Development (Cambridge, England) High 21937598
2020 Pituitary-specific deletion of Isl1 causes hypopituitarism with increased stem cell apoptosis, reduced differentiation of thyrotropes and gonadotropes, and 100% penetrant Rathke's cleft-like cysts with ectopic Foxa1 and Foxj1 expression, establishing ISL1 as driving pituitary progenitor differentiation into thyrotrope and gonadotrope lineages. Conditional KO (pituitary-specific Cre/loxP), gene expression analysis, histology The Journal of clinical investigation High 32453714
2023 ISL1 controls alpha cell fate competence and beta cell maturation in the pancreas; Isl1 elimination results in complete loss of alpha cells, disrupted islet architecture, and downregulation of beta cell maturation markers. Mechanistically, Isl1 deletion alters H3K27me3 histone modifications in promoter regions of endocrine differentiation genes. Transgenic mouse conditional KO, RNA-seq, H3K27me3 ChIP-seq (epigenomic profiling), ATAC-seq Cell & bioscience High 36899442
2024 EphrinB2 activates CDK5-dependent ISL1 nuclear translocation in lymphatic endothelial cells; nuclear ISL1 enhances transcription at the VEGFR3 (FLT4) promoter, promoting cardiac lymphangiogenesis. VEGFR3 inhibition abolishes EphrinB2-mediated lymphangiogenesis. EphrinB2 KO and overexpression in mice, CDK5 activity assay, ISL1 subcellular localization (nuclear translocation), ChIP (VEGFR3 promoter), VEGFR3 inhibitor pharmacology Signal transduction and targeted therapy Medium 39557830
2006 ISL1 and Lhx3, together with steroidogenic factor 1 (SF-1), activate the rat GnRH-R gene promoter in gonadotrope cells; ISL1 and Lhx3 bind cis-acting elements in the GnRH-R promoter (identified by transient transfection and DNA/protein interaction assays), and ISL1 activity in this context depends on SF-1 binding. This represents the first identified ISL1 transcriptional target in the anterior pituitary. Transient transfection reporter assay, DNA/protein interaction assay (EMSA), dominant-negative LHX3, deletion analysis, transgenic reporter mouse Molecular endocrinology (Baltimore, Md.) Medium 16613990
2022 ISL1 regulates the molecular and cellular features of spiral ganglion auditory neurons including neurogenesis, axonogenesis, migration, and neurotransmission; ISL1-deficient spiral ganglion neurons migrate aberrantly and cochlear wiring and tonotopic projections are profoundly disrupted. Neurod1-Cre conditional KO of Isl1 in auditory neurons, transcriptome analysis, neuroanatomical tracing, auditory brainstem response Proceedings of the National Academy of Sciences of the United States of America High 36074819
2021 ISL1 promotes neuroblastoma cell proliferation, EMT, and tumorigenesis by upregulating Aurora kinase A (AURKA), which activates PI3K/AKT signaling; blockade of AURKA attenuates the effects of ISL1 overexpression on proliferation and migration. ISL1 knockdown/overexpression (in vitro and in vivo xenograft), AURKA expression analysis, PI3K/AKT pathway analysis, AURKA pharmacological inhibition Cell death & disease Medium 34131100
2014 ISL1 activates c-Myc expression in non-Hodgkin lymphoma by directly binding a conserved site on the c-Myc enhancer (ChIP); ISL1 participates with p-STAT3 and p-c-Jun to form a p-STAT3/p-c-Jun/ISL1 transcriptional complex that binds directly to the ISL1 promoter, constituting a positive feedback loop for ISL1 expression. ChIP, Co-IP, ChIP-re-IP, luciferase assay, reporter assay Molecular cancer Medium 25070240
2013 ISL1 kidney-specific deletion causes kidney agenesis/hypoplasia and hydroureter due to ectopic/accessory ureteric bud formation; ISL1 is expressed in mesenchymal cells surrounding the ureteric bud base, and its deletion reduces Bmp4 expression in the metanephric region prior to ureteric budding. Conditional KO (Cre/loxP), in situ hybridization, gene expression analysis Journal of the American Society of Nephrology Medium 23641053
2020 ISL1 induces Gcn5 binding to GATA4/Nkx2.5 promoter regions and mediates interactions among Gcn5, HDAC1, G9A, and DNMT-1 at these promoters to upregulate GATA4/Nkx2.5 expression and promote MSC differentiation into cardiomyocytes; inhibition of Gcn5 blocks ISL1-induced differentiation. ChIP, co-IP, pharmacological inhibition (MB-3 to inhibit Gcn5), reporter assay, cardiomyocyte differentiation assay Scientific reports Medium 32019948

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature 653 1691825
2009 Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature 413 19571884
1991 The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat. Neuron 322 1764243
2007 The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway. Cell stem cell 253 18371348
1993 Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation. Development (Cambridge, England) 230 8223269
1994 Developmental regulation of islet-1 mRNA expression during neuronal differentiation in embryonic zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 214 8167375
2007 Wnt/beta-catenin signaling promotes expansion of Isl-1-positive cardiac progenitor cells through regulation of FGF signaling. The Journal of clinical investigation 213 17607356
2007 Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proceedings of the National Academy of Sciences of the United States of America 194 17519333
2008 Islet1 cardiovascular progenitors: a single source for heart lineages? Development (Cambridge, England) 191 18156162
2009 A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nature cell biology 186 19620969
2008 A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nature neuroscience 169 18849985
2008 ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells. Development (Cambridge, England) 157 18434421
2008 The contribution of Islet1-expressing splanchnic mesoderm cells to distinct branchiomeric muscles reveals significant heterogeneity in head muscle development. Development (Cambridge, England) 142 18184728
2008 Gene regulation logic in retinal ganglion cell development: Isl1 defines a critical branch distinct from but overlapping with Pou4f2. Proceedings of the National Academy of Sciences of the United States of America 129 18460603
2008 Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochemical and biophysical research communications 116 18722343
1992 The LIM family transcription factor Isl-1 requires cAMP response element binding protein to promote somatostatin expression in pancreatic islet cells. Proceedings of the National Academy of Sciences of the United States of America 115 1352885
2009 Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes 112 19502415
2007 Expression of the LIM-homeodomain protein Isl1 in the developing and mature mouse retina. The Journal of comparative neurology 112 17480014
2008 Islet 1 (Isl1) expression is a reliable marker for pancreatic endocrine tumors and their metastases. The American journal of surgical pathology 110 18300808
2004 Expression of Islet1 marks the sensory and neuronal lineages in the mammalian inner ear. The Journal of comparative neurology 110 15329890
1993 The cysteine-rich LIM domains inhibit DNA binding by the associated homeodomain in Isl-1. The EMBO journal 107 7901000
2006 Islet1 and Islet2 have equivalent abilities to promote motoneuron formation and to specify motoneuron subtype identity. Development (Cambridge, England) 100 16672347
2015 Transcription factor ISL1 is essential for pacemaker development and function. The Journal of clinical investigation 97 26193633
2012 Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. Proceedings of the National Academy of Sciences of the United States of America 93 23093675
1995 The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription. The Journal of biological chemistry 92 7759514
2015 Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate. Proceedings of the National Academy of Sciences of the United States of America 91 25775587
2019 Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate. Cell research 82 31024170
2003 Role of Islet1 in the patterning of murine dentition. Development (Cambridge, England) 80 12900460
1991 Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1. Molecular endocrinology (Baltimore, Md.) 74 1685766
2013 Nkx2-5(+)islet1(+) mesenchymal precursors generate distinct spleen stromal cell subsets and participate in restoring stromal network integrity. Immunity 73 23601687
2014 Islet-1 Is essential for pancreatic β-cell function. Diabetes 72 25028525
2015 Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity. Stem cells (Dayton, Ohio) 69 25524439
2011 ISL1 promotes pancreatic islet cell proliferation. PloS one 69 21829621
2019 Isl1-expressing non-venous cell lineage contributes to cardiac lymphatic vessel development. Developmental biology 68 31112709
2006 Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochemical and biophysical research communications 68 16713999
2008 Islet1 as a marker of subdivisions and cell types in the developing forebrain of Xenopus. Neuroscience 59 18515014
2022 Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy. ACS applied materials & interfaces 58 35920579
2004 Islet-1 expression in the developing chicken inner ear. The Journal of comparative neurology 53 15281076
2012 Islet1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos. Development (Cambridge, England) 50 22438573
2011 Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice. Development (Cambridge, England) 48 21937598
1996 Activation of amylin gene transcription by LIM domain homeobox gene isl-1. Molecular endocrinology (Baltimore, Md.) 45 8833653
2013 Expression of Isl1 during mouse development. Gene expression patterns : GEP 44 23906961
2012 A novel Rho-dependent pathway that drives interaction of fascin-1 with p-Lin-11/Isl-1/Mec-3 kinase (LIMK) 1/2 to promote fascin-1/actin binding and filopodia stability. BMC biology 43 22883572
2006 The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor 1 to enhance gonadotrope-specific activity of the gonadotropin-releasing hormone receptor gene promoter. Molecular endocrinology (Baltimore, Md.) 43 16613990
2000 The LIM/homeodomain protein islet-1 modulates estrogen receptor functions. Molecular endocrinology (Baltimore, Md.) 42 11043578
2019 Isl1 Regulation of Nkx2.1 in the Early Foregut Epithelium Is Required for Trachea-Esophageal Separation and Lung Lobation. Developmental cell 41 31813798
2018 Revised roles of ISL1 in a hES cell-based model of human heart chamber specification. eLife 40 29337667
2016 ISL1 and JMJD3 synergistically control cardiac differentiation of embryonic stem cells. Nucleic acids research 38 27105846
2007 Biology of Isl1+ cardiac progenitor cells in development and disease. Cellular and molecular life sciences : CMLS 38 17380308
2012 ISL1 directly regulates FGF10 transcription during human cardiac outflow formation. PloS one 37 22303449
2014 Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells. PloS one 36 24643061
2018 Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification. Cell death & disease 35 29445148
2022 ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization. Proceedings of the National Academy of Sciences of the United States of America 34 36074819
2014 Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons. Gene expression patterns : GEP 33 24709358
2011 Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development. The Journal of biological chemistry 33 21388963
2007 Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression. Development (Cambridge, England) 33 17376808
2014 Impaired enteroendocrine development in intestinal-specific Islet1 mouse mutants causes impaired glucose homeostasis. American journal of physiology. Gastrointestinal and liver physiology 32 25214396
2013 Hair cell overexpression of Islet1 reduces age-related and noise-induced hearing loss. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 24048839
2010 prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons. Genesis (New York, N.Y. : 2000) 30 20836130
2021 ISL1 promoted tumorigenesis and EMT via Aurora kinase A-induced activation of PI3K/AKT signaling pathway in neuroblastoma. Cell death & disease 29 34131100
2012 CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy. Circulation research 29 22343712
2024 EphrinB2-mediated CDK5/ISL1 pathway enhances cardiac lymphangiogenesis and alleviates ischemic injury by resolving post-MI inflammation. Signal transduction and targeted therapy 27 39557830
2012 Islet1-expressing cardiac progenitor cells: a comparison across species. Development genes and evolution 27 22526874
2017 ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development. Scientific reports 26 28176844
2013 miR-128 regulates non-myocyte hyperplasia, deposition of extracellular matrix and Islet1 expression during newt cardiac regeneration. Developmental biology 26 24055866
2011 Islet1 selectively promotes peripheral axon outgrowth in Rohon-Beard primary sensory neurons. Developmental dynamics : an official publication of the American Association of Anatomists 26 21108318
1995 Presence of isl-1-related LIM domain homeobox genes in teleost and their similar patterns of expression in brain and spinal cord. The Journal of biological chemistry 26 7852419
2015 Expression and function of the LIM-homeodomain transcription factor Islet-1 in the developing and mature vertebrate retina. Experimental eye research 25 26122047
2012 Tup/Islet1 integrates time and position to specify muscle identity in Drosophila. Development (Cambridge, England) 25 22949613
2005 The LIM/homeodomain protein Islet1 recruits Janus tyrosine kinases and signal transducer and activator of transcription 3 and stimulates their activities. Molecular biology of the cell 25 15659653
2014 ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex. Molecular cancer 24 25070240
2010 Electrical activation of sinus venosus myocardium and expression patterns of RhoA and Isl-1 in the chick embryo. Journal of cardiovascular electrophysiology 24 20455990
2021 The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome. International journal of molecular sciences 23 33808224
2019 Value of SATB2, ISL1, and TTF1 to differentiate rectal from other gastrointestinal and lung well-differentiated neuroendocrine tumors. Pathology, research and practice 23 31133441
2019 Islet1 and Brn3 Expression Pattern Study in Human Retina and hiPSC-Derived Retinal Organoid. Stem cells international 23 31885629
2013 Islet1 deletion causes kidney agenesis and hydroureter resembling CAKUT. Journal of the American Society of Nephrology : JASN 23 23641053
2008 Expression of Islet1 in thyroid development related to budding, migration, and fusion of primordia. Developmental dynamics : an official publication of the American Association of Anatomists 23 18985716
1994 The LIM domain homeobox gene isl-1: conservation of human, hamster, and rat complementary deoxyribonucleic acid sequences and expression in cell types of nonneuroendocrine lineage. Endocrinology 23 7907017
2020 microRNA-9 and -29a regulate the progression of diabetic peripheral neuropathy via ISL1-mediated sonic hedgehog signaling pathway. Aging 22 32544883
2020 Identifying Isl1 Genetic Lineage in the Developing Olfactory System and in GnRH-1 Neurons. Frontiers in physiology 21 33192618
2019 A New ISL1 Loss-of-Function Mutation Predisposes to Congenital Double Outlet Right Ventricle. International heart journal 21 31484864
2018 ISL1 loss-of-function mutation contributes to congenital heart defects. Heart and vessels 21 30390123
2017 ISLET1-Dependent β-Catenin/Hedgehog Signaling Is Required for Outgrowth of the Lower Jaw. Molecular and cellular biology 21 28069742
2002 Positional candidate gene analysis of Lim domain homeobox gene (Isl-1) on chromosome 5q11-q13 in a French morbidly obese population suggests indication for association with type 2 diabetes. Diabetes 20 11978668
2019 Adult islet1 Expression Outlines Ventralized Derivatives Along Zebrafish Neuraxis. Frontiers in neuroanatomy 19 30863287
2018 ISL1 is upregulated in breast cancer and promotes cell proliferation, invasion, and angiogenesis. OncoTargets and therapy 19 29497310
2018 ISL1 promotes cancer progression and inhibits cisplatin sensitivity in triple-negative breast cancer cells. International journal of molecular medicine 19 30226569
2015 SSBP3 Interacts With Islet-1 and Ldb1 to Impact Pancreatic β-Cell Target Genes. Molecular endocrinology (Baltimore, Md.) 19 26495868
2023 ISL1 controls pancreatic alpha cell fate and beta cell maturation. Cell & bioscience 18 36899442
2018 The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine carcinomas. Annals of diagnostic pathology 18 30236546
2017 Isl1 Controls Patterning and Mineralization of Enamel in the Continuously Renewing Mouse Incisor. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 18 28650075
2016 ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons. Scientific reports 18 27819291
2021 Identification of variants of ISL1 gene promoter and cellular functions in isolated ventricular septal defects. American journal of physiology. Cell physiology 17 34260301
2015 Embryonic Origin of the Islet1 and Pax6 Neurons of the Chicken Central Extended Amygdala Using Cell Migration Assays and Relation to Different Neuropeptide-Containing Cells. Brain, behavior and evolution 17 26022433
2021 Spotlight on Isl1: A Key Player in Cardiovascular Development and Diseases. Frontiers in cell and developmental biology 16 34901033
2020 Islet-1 synergizes with Gcn5 to promote MSC differentiation into cardiomyocytes. Scientific reports 16 32019948
2020 Rathke's cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors. The Journal of clinical investigation 16 32453714
2013 LIM-homeodomain transcription factor Isl-1 mediates the effect of leptin on insulin secretion in mice. The Journal of biological chemistry 16 23504315
2023 Endoderm-derived islet1-expressing cells differentiate into endothelial cells to function as the vascular HSPC niche in zebrafish. Developmental cell 15 36693371
2019 Collaborative ISL1/GATA3 interaction in controlling neuroblastoma oncogenic pathways overlapping with but distinct from MYCN. Theranostics 15 30867811

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