Affinage

PCF11

Pre-mRNA cleavage complex 2 protein Pcf11 · UniProt O94913

Length
1555 aa
Mass
173.1 kDa
Annotated
2026-04-29
31 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCF11 is a conserved core subunit of the cleavage/polyadenylation machinery that couples RNA polymerase II transcription termination to 3'-end processing of mRNAs and non-coding RNAs. Its N-terminal CTD-interaction domain (CID) binds phosphorylated Pol II CTD repeats by induced fit, enabling PCF11 to bridge the polymerase to the nascent transcript and dismantle elongation complexes without nucleotide hydrolysis—a mechanism conserved from yeast to metazoans (PMID:15998810, PMID:16387654, PMID:15665873). PCF11 operates genome-wide at sub-stoichiometric levels relative to the CPA complex: it stimulates premature cleavage/polyadenylation to attenuate transcriptional regulators, autoregulates its own abundance via intronic polyadenylation, and modulates alternative polyadenylation in a gene-size-dependent manner, with functional consequences for neurodifferentiation and HIV-1 latency (PMID:30819644, PMID:30840896, PMID:30552333, PMID:38015843). Its activity is tuned by WNK1 phosphorylation of the CID (promoting transcript release and mRNA export), by the cap modification m6Am (which sequesters PCF11 to suppress premature termination), and by condensate formation with unphosphorylated Spt5 facilitated by PP1/PNUTS phosphatase during termination and piRNA-guided silencing (PMID:29196535, PMID:39481383, PMID:40015272).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    Identification of PCF11 as an essential subunit of yeast Cleavage Factor IA established that the CPA machinery contains a dedicated factor required for both cleavage and polyadenylation, and linked it to Rna14/Rna15.

    Evidence Two-hybrid screen, co-fractionation, in vitro cleavage/polyadenylation assay with antibody neutralization, and thermosensitive mutant analysis in S. cerevisiae

    PMID:9032237

    Open questions at the time
    • Mechanism by which Pcf11 contributes to catalytic steps unknown
    • No structural information on Pcf11 or its domains
  2. 2005 High

    Structural and biochemical work revealed that the Pcf11 CID binds phosphorylated Pol II CTD by induced fit and that this bridging interaction is sufficient to dismantle elongation complexes without nucleotide hydrolysis, establishing a direct termination mechanism.

    Evidence NMR structure of CID–CTD complex; in vitro elongation complex dismantling assay with purified yeast Pol II and CID mutants

    PMID:15665873 PMID:15998810

    Open questions at the time
    • Termination mechanism validated only in vitro; genome-wide role not yet tested
    • No metazoan confirmation
  3. 2006 High

    Extension to Drosophila demonstrated that PCF11-mediated termination is conserved in metazoans and showed that PCF11 preferentially dismantles paused complexes, while structural work revealed the Clp1–PCF11 interface and a competition between CTD and RNA binding at the CID.

    Evidence RNAi knockdown with ChIP readthrough in Drosophila; in vitro elongation complex dismantling; NMR competition assays; Clp1–Pcf11 crystal structure

    PMID:16387654 PMID:16497660 PMID:17151076

    Open questions at the time
    • Human in vivo termination role not yet shown
    • Functional significance of CID RNA-binding competition untested in vivo
  4. 2007 Medium

    Human PCF11 was shown to be required for Pol II termination and downstream RNA degradation in HeLa cells, establishing functional conservation in humans.

    Evidence siRNA knockdown with RT-PCR and nuclear run-on assays in HeLa cells

    PMID:18086705

    Open questions at the time
    • Single-lab result
    • No genome-wide assessment of human termination defects
  5. 2011 High

    Dissection of the Clp1–Pcf11 interface demonstrated that disruption of this contact impairs both 3'-end processing and termination in vivo, establishing Clp1 as a structural bridge between CF IA and CPF that requires Pcf11 contact for function.

    Evidence Yeast genetics, co-immunoprecipitation, in vitro processing assays with Clp1 ATP-binding and Pcf11 interaction mutants

    PMID:21993299

    Open questions at the time
    • Whether the Clp1–Pcf11 interaction is regulated by signaling unknown
    • Human Clp1–PCF11 interface not functionally validated
  6. 2015 High

    Pcf11 was placed in the NRD-dependent ncRNA termination pathway downstream of Nrd1: an exchange of Nrd1 for Pcf11 on chromatin facilitates CTD Ser2 phosphorylation and Sen1 recruitment, revealing how two termination pathways are coordinated.

    Evidence ChIP-seq, RNA-seq, and genetic analysis with CID mutants in S. cerevisiae

    PMID:25877920

    Open questions at the time
    • Metazoan equivalent of Nrd1 pathway and Pcf11's role therein uncharacterized
    • Kinase responsible for Ser2-P increase upon Pcf11 recruitment not identified
  7. 2016 High

    Structural characterization of two Pcf11 zinc-finger domains flanking the Clp1-binding region resolved their distinct contributions to cleavage versus polyadenylation, separating these two functions within a single subunit.

    Evidence X-ray crystallography, NMR, in vitro cleavage/polyadenylation assays, and yeast genetic complementation

    PMID:27780845 PMID:28973460

    Open questions at the time
    • Zinc-finger binding partners/substrates unidentified
    • Whether zinc fingers contribute to termination per se unclear
  8. 2017 High

    WNK1 kinase was identified as a regulator of PCF11: phosphorylation of the CID weakens Pol II CTD interaction, promoting transcript release and mRNA export, revealing a signaling input into the termination machinery.

    Evidence In vitro kinase assay, co-immunoprecipitation, chromatin RNA-seq, and mRNA export assay in mammalian cells

    PMID:29196535

    Open questions at the time
    • Physiological signals controlling WNK1 nuclear activity not defined
    • Whether other kinases phosphorylate the CID not tested
  9. 2019 High

    Genome-wide studies in vertebrates established that PCF11 operates at sub-stoichiometric levels to stimulate premature termination, autoregulates via intronic polyadenylation, modulates alternative polyadenylation in a gene-size-dependent manner, and shapes neurodifferentiation programs in neuroblastoma.

    Evidence mNET-seq, 3' mRNA-seq, ChIP-seq, PCF11 depletion in human cells, zebrafish CRISPR/morpholino knockdown; RNAi screening in neuroblastoma lines with functional proliferation/apoptosis assays

    PMID:30552333 PMID:30819644 PMID:30840896

    Open questions at the time
    • How sub-stoichiometric PCF11 is selectively targeted to specific genes unknown
    • Structural basis for IPA autoregulation not resolved
  10. 2023 High

    PCF11 was found to enforce HIV-1 latency by promoting premature termination at the proviral promoter independently of the CPA complex, acting interdependently with WDR82 on a shared pathway.

    Evidence Co-immunoprecipitation, ChIP-seq, siRNA knockdown with HIV-1 reactivation assays in latently infected T cells

    PMID:38015843

    Open questions at the time
    • How PCF11 terminates HIV-1 transcription without canonical CPA machinery not mechanistically resolved
    • Whether PCF11–WDR82 complex acts at other loci unknown
  11. 2024 High

    PCF11 was identified as a reader of the cap modification m6Am, which sequesters PCF11 near the TSS to suppress premature termination—establishing an epitranscriptomic layer of termination control with implications for MYCN repression in neuroblastoma.

    Evidence Quantitative proteomics with m6Am-modified RNA pulldown, nascent and mature RNA quantification, PCF11 knockdown, and m6Am depletion in neuroblastoma cells

    PMID:39481383

    Open questions at the time
    • Structural basis of m6Am recognition by PCF11 not determined
    • Genome-wide impact of m6Am-PCF11 axis beyond neuroblastoma unexplored
  12. 2025 High

    Condensate formation between Pcf11 and unphosphorylated Spt5, facilitated by PP1/PNUTS phosphatase, was shown to stall Pol II during termination and piRNA-guided silencing in Drosophila, introducing phase separation as a termination mechanism; separately, SPT6 was identified as recruiting PNUTS and PCF11 to Pol II for termination in human cells.

    Evidence RNAi screening, tethering assays, phase separation/condensate assays, Pol II ChIP, and piRNA pathway epistasis in Drosophila; siRNA knockdown with ChIP-seq and RNA-seq in human cells

    PMID:40015272 PMID:40103229

    Open questions at the time
    • Whether PCF11 condensate formation occurs in mammalian termination not tested
    • How SPT6 recruits PCF11 at the molecular level unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of the PCF11–m6Am interaction, the mechanism by which sub-stoichiometric PCF11 selects specific gene targets for premature termination, whether PCF11 condensate-mediated termination operates in mammals, and how the multiple regulatory inputs (WNK1 phosphorylation, m6Am, Spt5 phosphorylation state) are integrated at individual loci.
  • No structural model for m6Am recognition
  • Gene-target selectivity mechanism unknown
  • Condensate function in mammalian termination untested
  • Integration of multiple regulatory inputs at single loci unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 4 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 2 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-8953854 Metabolism of RNA 5 R-HSA-1266738 Developmental Biology 2 R-HSA-9609507 Protein localization 1
Partners
CLP1PNUTSRNA14RNA15SPT5SPT6WDR82WNK1
Complex memberships
CF IA (Cleavage Factor IA)CPA complex (Cleavage and Polyadenylation)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 PCF11 encodes an essential protein component of yeast Cleavage Factor I (CF I), required for pre-mRNA cleavage and polyadenylation. Thermosensitive pcf11 mutations cause shortening of poly(A) tails and decreased mRNA levels; antibody neutralization of Pcf11 abolishes cleavage and polyadenylation in vitro. Pcf11 co-fractionates with Rna15 in CF I fractions and was identified via two-hybrid interaction with Rna14 and Rna15. Two-hybrid screen, co-fractionation by anion-exchange chromatography, in vitro cleavage/polyadenylation assay with antibody neutralization, thermosensitive mutant analysis Molecular and cellular biology High 9032237
2005 A 140-amino acid fragment of yeast Pcf11 containing the CTD-interaction domain (CID) dismantles elongating RNA Pol II complexes in vitro by bridging the CTD to the nascent transcript, causing dissociation of both Pol II and transcript from DNA without nucleotide hydrolysis. This mechanism requires both the CTD of the Pol II largest subunit and the CID of Pcf11. In vitro elongation complex dismantling assay using purified yeast Pol II; CID mutant analysis Genes & development High 15998810
2005 The Pcf11 CTD-interacting domain (CID) binds phosphorylated Pol II CTD heptad repeats by induced fit: the disordered phospho-CTD adopts a structured conformation upon binding to Pcf11 CID. Binding is regulated by CTD phosphorylation and proline cis-trans isomerization (only the all-trans CTD proline form is selected). NMR spectroscopy, structural and biophysical interaction analyses Nature structural & molecular biology High 15665873
2006 Drosophila Pcf11 (dPcf11) is directly involved in transcription termination in metazoans: it localizes to the 3' end of the hsp70 gene and to most transcribed loci on polytene chromosomes. RNAi depletion causes Pol II readthrough at normal termination sites. Biochemically, dPcf11 dismantles elongation complexes by bridging the CTD to RNA in a CTD-dependent but nucleotide-independent manner, and preferentially dismantles paused (low nucleotide) elongation complexes. RNAi knockdown with Pol II ChIP readthrough assay; immunolocalization on polytene chromosomes; in vitro elongation complex dismantling assay Molecular cell High 16387654
2006 The Pcf11 CID also weakly binds RNA, and CTD phosphopeptides compete with RNA for the same binding surface on the CID. This competition between CTD and RNA at the CID is proposed to be mechanistically important for disengaging polyadenylation factors from Pol II. NMR chemical shift perturbation and competitive binding assays with CTD phosphopeptides and RNA RNA (New York, N.Y.) Medium 16497660
2006 Crystal structure of a ternary Clp1–ATP–Pcf11 complex reveals that Clp1 contains three domains with a central ATP-binding site resembling SIMIBI-class ATPases but without hydrolysis activity. Three conserved Pcf11 residues mediate the Clp1–Pcf11 interaction at the central domain, maintaining coupling between the nucleotide-binding subunit and the polyadenylation machinery. X-ray crystallography; ATPase activity assay Nucleic acids research High 17151076
2007 Human PCF11 (hPcf11) is required for efficient transcription termination by Pol II and for degradation of the downstream 3' cleavage product of the poly(A) site in human (HeLa) cells. Both functions require an intact poly(A) signal. siRNA knockdown in HeLa cells; RT-PCR and nuclear run-on termination assays; RNA processing assays Nucleic acids research Medium 18086705
2011 Yeast Clp1 interacts with the CPF complex through its N-terminal and central domains, bridging CF IA and CPF. Mutations in the Clp1 ATP-binding site that displace ATP do not affect ATP binding per se but disrupt the Clp1–Pcf11 interaction, and a Pcf11 mutation that disrupts the Clp1 contact causes defects in 3'-end processing and transcription termination in vivo. Yeast genetics, growth assays, in vitro 3'-end processing assays, co-immunoprecipitation Nucleic acids research High 21993299
2015 In S. cerevisiae, Pcf11 is generally required for NRD-dependent transcription termination of short ncRNAs, acting downstream of Nrd1. Pcf11 recruitment depends on Nrd1, and mutation of the Pcf11 CID causes Nrd1 retention on chromatin, delayed ncRNA degradation, restricted Pol II CTD Ser2 phosphorylation, and impaired Sen1–Pol II interaction. An exchange of Nrd1 and Pcf11 on chromatin facilitates Pol II pausing and CTD Ser2-P phosphorylation required for Sen1-dependent NRD termination. ChIP-seq, RNA-seq, genetic analysis with CID mutants, chromatin fractionation Genes & development High 25877920
2016 The C-terminal domain of Pcf11 (conserved from yeast to humans) forms a novel zinc-finger fold resembling a trillium flower. A conserved surface on this zinc finger is required for both cleavage and polyadenylation activities, as determined by structural, biochemical, and genetic analyses. X-ray crystallography, NMR, in vitro cleavage/polyadenylation assay, yeast genetics RNA (New York, N.Y.) High 27780845
2017 Yeast Pcf11 contains two separate Zn2+-binding zinc-finger domains flanking the Clp1-recognition region. These zinc-finger domains are not required for CF IA assembly or Pol II termination but contribute to different extents to pre-mRNA 3'-end cleavage and polyadenylation. Structural characterization (NMR/X-ray), mass spectrometry, in vitro cleavage/polyadenylation assays, yeast genetic complementation Nucleic acids research High 28973460
2017 Nuclear-localized WNK1 kinase phosphorylates the PCF11 CID, which weakens PCF11's interaction with Pol II CTD. This phosphorylation event promotes transcript release from chromatin-associated Pol II and facilitates mRNA export to the cytoplasm. In vitro kinase assay, co-immunoprecipitation, chromatin RNA-seq, mRNA export assay in mammalian cells Genes & development High 29196535
2019 Vertebrate PCF11 enhances transcription termination and stimulates early (premature) cleavage and polyadenylation genome-wide. PCF11 preferentially binds between closely spaced genes to prevent transcriptional interference. PCF11 is sub-stoichiometric to the CPA complex and autoregulates its own levels via premature termination of its own transcript. PCF11 selectively attenuates transcriptional regulators by premature CPA/termination and is essential for vertebrate development. mNET-seq, 3' mRNA-seq, chromatin RNA-seq, ChIP-seq, PCF11 depletion in human cells and zebrafish CRISPR/morpholino knockdown Molecular cell High 30819644
2019 PCF11 modulates gene expression according to gene size: downregulation of PCF11 inhibits short gene expression while upregulating long genes by suppressing intronic polyadenylation (IPA) enriched in large introns. PCF11 autoregulates itself through a conserved IPA site; removing this IPA site leads to global activation of promoter-proximal poly(A) sites. siRNA knockdown, 3' mRNA-seq (poly(A)-seq), CRISPR deletion of IPA site, cell differentiation assays Cell reports High 30840896
2018 PCF11 is a critical regulator of alternative polyadenylation (APA) in neuroblastoma, directing APA of hundreds of transcripts including a differentiation RNA-operon. PCF11 shapes inputs converging on WNT signaling and governs cell cycle, proliferation, apoptosis, and neurodifferentiation. Postnatal PCF11 downregulation induces a neurodifferentiation program. Extensive RNAi screening, 3' mRNA-seq, functional assays for proliferation/apoptosis/differentiation in neuroblastoma cell lines Nature communications High 30552333
2023 PCF11 represses HIV-1 transcription by promoting premature transcription termination independently of the CPA complex or the 5' LTR poly(A) signal. PCF11 interacts with WDR82, and together they are recruited interdependently to the promoter-proximal region of the HIV-1 provirus. Knockdown of PCF11 or WDR82 reactivates HIV-1 expression in latently infected cells, and they act on the same pathway. Co-immunoprecipitation, ChIP-seq, siRNA knockdown in latently infected T cells, HIV-1 reactivation assay Proceedings of the National Academy of Sciences of the United States of America High 38015843
2024 PCF11 is identified as a reader of the cap-specific RNA modification m6Am (N6,2'-O-dimethyladenosine). m6Am sequesters PCF11 away from proximal Pol II near transcription start sites, suppressing PCF11-mediated premature transcription termination and promoting full-length transcription. This anti-terminator function is enhanced when PCF11 levels are reduced (as during neuroblastoma differentiation therapy), and it operates through ATF3 upregulation to repress MYCN. Quantitative proteomics (m6Am-modified RNA pulldown), direct quantification of mature vs. nascent RNA, PCF11 knockdown, m6Am depletion assays in neuroblastoma cells Molecular cell High 39481383
2025 In Drosophila germ line, Pcf11 and Spt5 form condensates that stall RNA Pol II to facilitate transcription termination and piRNA-guided heterochromatin formation. Pcf11 enforced tethering causes co-transcriptional repression and Pol II stalling dependent on an α-helical condensate-forming region. Pcf11 preferentially forms condensates with unphosphorylated Spt5, promoted by PP1/PNUTS phosphatase activity during termination. RNAi screening, tethering assays, phase separation/condensate assays, Pol II ChIP, piRNA pathway genetic epistasis Molecular cell High 40015272
2025 PCF11 collaborates with SPT6 and PNUTS in transcription termination: SPT6 depletion causes readthrough transcription, and SPT6 facilitates termination by recruiting PNUTS and PCF11 to Pol II. SPT6 and PNUTS jointly restrict PROMPTs, while PCF11 presence is required for PROMPT accumulation at hundreds of genes in the absence of SPT6. siRNA knockdown, ChIP-seq, RNA-seq for readthrough and PROMPT detection in human cells Nucleic acids research Medium 40103229
2025 PCF11 and Cbc (the two components of Cleavage Factor complex II) change subnuclear localization during male germ cell differentiation in Drosophila, moving from homogeneous nuclear distribution in spermatogonia to concentrated around the nucleolus in later spermatocyte stages, coinciding with developmentally regulated 3'UTR shortening via alternative polyadenylation. Immunofluorescence, confocal microscopy in Drosophila spermatocytes microPublication biology Medium 40896257
2025 PCF11 interacts with swine influenza virus NP protein to promote viral polymerase activity, facilitating vRNP assembly and viral mRNA synthesis. PCF11 negatively regulates the IFN-β signaling pathway, further facilitating RNA virus replication. Co-immunoprecipitation, viral polymerase activity assay, siRNA knockdown, IFN-β reporter assay Microbiological research Medium 40252262

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination. Molecular cell 116 30819644
2005 CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3'-end processing factor, Pcf11. Genes & development 112 15998810
2005 Key features of the interaction between Pcf11 CID and RNA polymerase II CTD. Nature structural & molecular biology 103 15665873
2006 Pcf11 is a termination factor in Drosophila that dismantles the elongation complex by bridging the CTD of RNA polymerase II to the nascent transcript. Molecular cell 89 16387654
1997 PCF11 encodes a third protein component of yeast cleavage and polyadenylation factor I. Molecular and cellular biology 88 9032237
2018 Transcriptome 3'end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma. Nature communications 86 30552333
2019 Regulation of Intronic Polyadenylation by PCF11 Impacts mRNA Expression of Long Genes. Cell reports 84 30840896
2015 Pcf11 orchestrates transcription termination pathways in yeast. Genes & development 67 25877920
2006 Structure of a nucleotide-bound Clp1-Pcf11 polyadenylation factor. Nucleic acids research 61 17151076
2007 Human Pcf11 enhances degradation of RNA polymerase II-associated nascent RNA and transcriptional termination. Nucleic acids research 50 18086705
2011 The interaction of Pcf11 and Clp1 is needed for mRNA 3'-end formation and is modulated by amino acids in the ATP-binding site. Nucleic acids research 28 21993299
2006 RNA polymerase II CTD phosphopeptides compete with RNA for the interaction with Pcf11. RNA (New York, N.Y.) 27 16497660
2017 WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription. Genes & development 18 29196535
2016 The C terminus of Pcf11 forms a novel zinc-finger structure that plays an essential role in mRNA 3'-end processing. RNA (New York, N.Y.) 17 27780845
2012 Identification of Inverse Regulator-a (Inr-a) as Synonymous with Pre-mRNA Cleavage Complex II Protein (Pcf11) in Drosophila. G3 (Bethesda, Md.) 16 22690379
2017 Distinct roles of Pcf11 zinc-binding domains in pre-mRNA 3'-end processing. Nucleic acids research 13 28973460
1992 The PCF1-1 mutation increases the activity of the transcription factor (TF) IIIB fraction from Saccharomyces cerevisiae. Nucleic acids research 12 1641338
2013 The regulatory role of Pcf11-similar-4 (PCFS4) in Arabidopsis development by genome-wide physical interactions with target loci. BMC genomics 11 24004414
2024 m6Am sequesters PCF11 to suppress premature termination and drive neuroblastoma differentiation. Molecular cell 10 39481383
2025 Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation. Molecular cell 8 40015272
2023 Premature transcription termination complex proteins PCF11 and WDR82 silence HIV-1 expression in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America 8 38015843
2009 Involvement of Pta1, Pcf11 and a KlCYC1 AU-rich element in alternative RNA 3'-end processing selection in yeast. FEBS letters 7 19646984
2015 Chemical shift assignments of a new folded domain from yeast Pcf11. Biomolecular NMR assignments 5 26133941
2022 PCF11, a Novel CD44-Downstream Transcriptional Target, Linking Its 3'-End Polyadenylation Function to Tumor Cell Metastasis. Frontiers in oncology 4 35756640
2024 Mutations in yeast Pcf11, a conserved protein essential for mRNA 3' end processing and transcription termination, elicit the Environmental Stress Response. Genetics 2 37967370
2024 Cap-specific m6Am modification: A transcriptional anti-terminator by sequestering PCF11 with implications for neuroblastoma therapy. Molecular cell 2 39515291
2025 Overlapping and distinct functions of SPT6, PNUTS, and PCF11 in regulating transcription termination. Nucleic acids research 1 40103229
2024 Computational insight into crucial interaction between Pcf11 and Ydh1 for pre-mRNA 3'-end processing. Journal of biomolecular structure & dynamics 1 39660558
2025 Pre-mRNA cleavage complex II protein Pcf11 facilitates swine influenza virus replication by interacting with viral NP and promoting polymerase activity. Microbiological research 0 40252262
2025 The CFII components PCF11 and Cbc change subnuclear localization as cells differentiate in the male germ line adult stem cell lineage. bioRxiv : the preprint server for biology 0 40777464
2025 The CFII components PCF11 and Cbc change subnuclear localization as cells differentiate in an adult stem cell lineage. microPublication biology 0 40896257