{"gene":"TEX10","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2015,"finding":"Tex10 physically interacts with Sox2 (identified via a protein interaction network surrounding Sox2) and is enriched at super-enhancers in a Sox2-dependent manner in embryonic stem cells, where it coordinates histone acetylation and DNA demethylation at super-enhancers to sustain pluripotency.","method":"Protein interaction network/Co-IP, ChIP, bisulfite sequencing, loss-of-function (shRNA knockdown) with pluripotency and reprogramming phenotypic readouts","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, ChIP occupancy, DNA methylation assays, and functional rescue experiments across mouse and human cells in one focused study","pmids":["25936917"],"is_preprint":false},{"year":2015,"finding":"Tex10 coordinates with Tet1 and p300 at super-enhancers to regulate histone acetylation and DNA demethylation, functioning as a core component of the pluripotency epigenetic regulatory complex.","method":"Co-IP/pulldown, ChIP-seq, loss-of-function assays in ESCs","journal":"Cell stem cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — ChIP-seq occupancy and Co-IP identifying complex components, multiple orthogonal methods in single focused study","pmids":["25936917","26046753"],"is_preprint":false},{"year":2017,"finding":"Tex10 physically interacts with Pcgf3 and Pcgf5 (polycomb group RING finger proteins) and with the transcriptional co-activator p300 in embryonic stem cells; Pcgf3/5 deletion substantially reduces Tex10 and p300 occupancy at target gene promoters, indicating Tex10 is recruited to these loci through Pcgf3/5.","method":"Proteomic/mass spectrometry interactome, Co-IP, ChIP-seq, CRISPR-Cas9 deletion of Pcgf3/5 with RNA-seq phenotypic readout","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — proteomic interactome plus Co-IP plus ChIP occupancy studies with genetic loss-of-function, multiple orthogonal methods","pmids":["29054931"],"is_preprint":false},{"year":2020,"finding":"TEX10 interacts with RELA (NF-κB subunit), increases its nuclear localization, and promotes RELA occupancy at target gene promoters (including TNFAIP8, SAT1, and IL6ST), thereby promoting colorectal cancer cell proliferation in an RELA-dependent manner.","method":"shRNA library screen, Co-IP, nuclear fractionation, ChIP, gene set enrichment analysis, in vitro and in vivo proliferation assays","journal":"Advanced science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP of interaction, ChIP showing RELA promoter occupancy, nuclear localization assay, and functional rescue/KD with defined molecular readouts in single study","pmids":["32995120"],"is_preprint":false},{"year":2018,"finding":"TEX10 knockdown in hepatocellular carcinoma cells decreases expression of stem cell markers and drug resistance, and TEX10 promotes cancer stemness through activation of the STAT3 signaling pathway.","method":"shRNA knockdown, Western blot, RT-qPCR, sphere formation, drug resistance assays with STAT3 pathway readouts","journal":"Cell cycle","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — loss-of-function with pathway readout, but mechanistic link to STAT3 is based on downstream marker analysis without direct interaction data in this paper","pmids":["30045663"],"is_preprint":false},{"year":2023,"finding":"TEX10 physically interacts with STAT3 (shown by Co-IP) and promotes p300-mediated STAT3 acetylation; p300 silencing abolishes TEX10-enhanced STAT3 transcriptional activity, establishing a TEX10–p300–STAT3 axis controlling HCC invasion and EMT.","method":"Co-immunoprecipitation, dual-luciferase reporter assay, ChIP, immunofluorescence, p300 siRNA silencing, transwell and xenograft assays","journal":"Molecular carcinogenesis","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, ChIP, reporter assay, and p300 rescue experiment provide multiple orthogonal methods supporting the mechanism in a single focused study","pmids":["37792308"],"is_preprint":false},{"year":2019,"finding":"TEX10 knockdown in esophageal squamous cell carcinoma cells inhibits proliferation, induces apoptosis and cell cycle arrest, reduces stemness and invasiveness, and suppresses EMT via inhibition of Wnt/β-catenin signaling.","method":"Lentiviral shRNA knockdown, CCK-8 proliferation assay, flow cytometry (apoptosis/cell cycle), Transwell assay, sphere formation, Western blot for β-catenin pathway components","journal":"Oncology reports","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — loss-of-function with pathway readouts, but mechanistic link to Wnt/β-catenin is based on downstream marker changes without direct interaction or ChIP data","pmids":["31638260"],"is_preprint":false},{"year":2021,"finding":"TEX10 stabilizes XRCC6 protein (Ku70) and thereby controls Wnt/β-catenin signaling and DNA repair pathways in bladder carcinoma; TEX10 knockout reduces radiotherapy resistance.","method":"Gene knockout, Western blot for XRCC6, in vitro and in vivo proliferation/metastasis assays, radiotherapy resistance assay","journal":"Journal of immunology research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, mechanism of TEX10–XRCC6 stabilization inferred without direct interaction data (no Co-IP or pulldown described in abstract)","pmids":["34966825"],"is_preprint":false},{"year":2025,"finding":"Tex10 binds to H3K4me3-marked promoters of Psmd3 and Psmd7 (negative regulators of Wnt signaling) and activates their expression, thereby restraining Wnt signaling during spermatogenesis and ESC-to-PGCLC differentiation; Tex10-null spermatocytes arrest at metaphase I, compromising round spermatid formation.","method":"Conditional knockout mouse model, dTAG-degron ESCs, bulk and single-cell RNA-seq, chromatin occupancy (ChIP or CUT&RUN), ESC-to-PGCLC differentiation assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO in vivo, chromatin occupancy at specific loci, single-cell transcriptomics, and functional differentiation assay with overexpression rescue; multiple orthogonal methods and replicated in peer-reviewed publication","pmids":["39988597"],"is_preprint":false},{"year":2023,"finding":"Tex10 binds Wnt negative regulator gene promoters marked by H3K4me3 at the PGCLC stage, and depletion or overexpression of Tex10 hyperactivates or attenuates Wnt signaling, respectively, resulting in compromised or enhanced PGCLC specification efficiency.","method":"Chromatin occupancy (ChIP), Tex10 conditional KO mice, single-cell RNA-seq, ESC-to-PGCLC differentiation assay, overexpression","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and genetic loss/gain-of-function with functional readout, but preprint status and overlap with published version (PMID 39988597) lower confidence","pmids":["36865339"],"is_preprint":true},{"year":2022,"finding":"LINC00624 and TEX10 form a co-regulatory axis that stimulates NF-κB activity to promote proliferation and migration of prostate cancer cells.","method":"In vitro knockdown assays, in vivo xenograft, NF-κB reporter/activity assay","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-regulatory axis described but molecular mechanism between LINC00624 and TEX10 not detailed in abstract; single lab, limited mechanistic depth","pmids":["35219000"],"is_preprint":false},{"year":2025,"finding":"TEX10 promotes expression of cell cycle regulators CDK2 and PCNA, increases S-phase entry, enhances differentiation marker genes MYOG and MYOD, and inhibits apoptosis in bovine myoblasts, with transcriptomic analysis implicating PI3K-Akt, cAMP, and IL-17 signaling pathways.","method":"CCK-8, EdU incorporation, qPCR, Western blot, immunofluorescence, flow cytometry (cell cycle), overexpression and knockdown, transcriptomic analysis","journal":"The international journal of biochemistry & cell biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single study in bovine cells, pathway involvement inferred from transcriptomics without direct mechanistic interrogation of pathway components","pmids":["40086620"],"is_preprint":false}],"current_model":"TEX10 is a transcriptional co-regulator that functions as a core component of the pluripotency network by physically associating with Sox2, Tet1, p300, and Pcgf3/5 to coordinate histone acetylation and DNA demethylation at super-enhancers in embryonic stem cells; in somatic and cancer contexts it activates NF-κB/RELA nuclear localization and STAT3 transcriptional activity (via p300-mediated STAT3 acetylation), while in germ cell development it binds H3K4me3-marked promoters of Wnt negative regulators (Psmd3/Psmd7) to restrain Wnt signaling and thereby enable spermatogenesis and primordial germ cell specification."},"narrative":{"mechanistic_narrative":"TEX10 is a chromatin-associated transcriptional co-regulator that operates within the embryonic stem cell pluripotency network and is repurposed as a transcriptional effector in germ cell development and cancer [PMID:25936917, PMID:39988597]. In embryonic stem cells it is identified through the Sox2 protein interaction network and is recruited to super-enhancers in a Sox2-dependent manner, where it acts together with Tet1 and the histone acetyltransferase p300 to coordinate histone acetylation and DNA demethylation that sustain pluripotency [PMID:25936917, PMID:26046753]. Its occupancy at target promoters is directed by the polycomb group RING finger proteins Pcgf3 and Pcgf5, whose deletion sharply reduces both TEX10 and p300 chromatin binding [PMID:29054931]. In germ cell development, Tex10 binds H3K4me3-marked promoters of the Wnt negative regulators Psmd3 and Psmd7 to activate their expression and thereby restrain Wnt signaling; its loss arrests spermatocytes at metaphase I and impairs primordial germ cell-like cell specification [PMID:39988597]. In cancer contexts TEX10 functions as a transcriptional amplifier: it physically interacts with the NF-κB subunit RELA to increase its nuclear localization and promoter occupancy in colorectal cancer [PMID:32995120], and it binds STAT3 to promote p300-mediated STAT3 acetylation and transcriptional activity driving hepatocellular carcinoma invasion [PMID:37792308].","teleology":[{"year":2015,"claim":"Establishing that TEX10 is a functional node of the pluripotency network answered whether it had a defined molecular role, placing it on Sox2-dependent super-enhancers controlling chromatin state.","evidence":"Sox2 interaction network with Co-IP, ChIP, bisulfite sequencing, and shRNA loss-of-function in mouse and human ESCs","pmids":["25936917","26046753"],"confidence":"High","gaps":["Direct catalytic activity of TEX10 itself not defined; it appears to act as a scaffold/recruiter rather than an enzyme","Whether super-enhancer recruitment requires Sox2 binding directly or an intermediary not resolved here"]},{"year":2017,"claim":"Identifying Pcgf3/5 as recruiters answered how TEX10 and p300 reach target promoters, linking a polycomb-associated module to TEX10 chromatin localization.","evidence":"Mass-spectrometry interactome, Co-IP, ChIP-seq, and CRISPR-Cas9 deletion of Pcgf3/5 with RNA-seq in ESCs","pmids":["29054931"],"confidence":"High","gaps":["Structural basis of the TEX10–Pcgf3/5 interaction unknown","Whether the same recruitment logic applies outside ESCs not tested"]},{"year":2018,"claim":"Linking TEX10 to cancer stemness extended its role beyond ESCs, implicating STAT3 signaling in hepatocellular carcinoma.","evidence":"shRNA knockdown with stem-cell marker, drug resistance, and STAT3 pathway readouts","pmids":["30045663"],"confidence":"Medium","gaps":["STAT3 link inferred from downstream markers without direct interaction data in this study","No chromatin occupancy data linking TEX10 to STAT3 targets"]},{"year":2019,"claim":"Connecting TEX10 to Wnt/β-catenin signaling in esophageal carcinoma broadened its pathway repertoire, presaging the Wnt-regulatory role later defined mechanistically in germ cells.","evidence":"Lentiviral shRNA knockdown with proliferation, apoptosis, EMT, and β-catenin Western blot readouts","pmids":["31638260"],"confidence":"Medium","gaps":["Mechanistic link to Wnt based on downstream markers without interaction or ChIP data","Directionality (TEX10 promotes vs. restrains Wnt) differs from germ cell findings, unresolved"]},{"year":2020,"claim":"Demonstrating a TEX10–RELA interaction answered how TEX10 couples to inflammatory transcription, showing it drives NF-κB nuclear localization and target occupancy in colorectal cancer.","evidence":"shRNA screen, Co-IP, nuclear fractionation, ChIP, and in vitro/in vivo proliferation assays","pmids":["32995120"],"confidence":"High","gaps":["How TEX10 increases RELA nuclear import mechanistically not defined","Whether p300 participates in this axis as it does for STAT3 not tested"]},{"year":2023,"claim":"Defining the TEX10–p300–STAT3 axis provided the direct molecular mechanism behind earlier STAT3 association, showing TEX10 promotes p300-mediated STAT3 acetylation.","evidence":"Reciprocal Co-IP, dual-luciferase reporter, ChIP, p300 siRNA rescue, transwell and xenograft assays","pmids":["37792308"],"confidence":"High","gaps":["Whether TEX10 directly bridges p300 and STAT3 or acts indirectly not structurally resolved","Relationship between this acetylation function and the ESC p300 module unexplored"]},{"year":2025,"claim":"Conditional knockout established TEX10's physiological function in germ cell development, showing it activates Psmd3/Psmd7 at H3K4me3 promoters to restrain Wnt and enable spermatogenesis.","evidence":"Conditional KO mice, dTAG-degron ESCs, bulk/single-cell RNA-seq, chromatin occupancy, and PGCLC differentiation with rescue","pmids":["39988597","36865339"],"confidence":"High","gaps":["How TEX10 reads or is recruited to H3K4me3-marked promoters not defined","Reconciliation of Wnt-restraining (germ cells) versus Wnt-promoting (cancer) roles unresolved"]},{"year":null,"claim":"The intrinsic biochemical activity of TEX10 — whether it possesses any catalytic function or acts purely as a scaffold/recruiter — remains undefined across all contexts.","evidence":"No discovery in the timeline assigns TEX10 a direct enzymatic activity","pmids":[],"confidence":"Low","gaps":["No structural model of TEX10 or its complexes","Mechanism of context-dependent partner selection (Pcgf3/5 vs RELA vs STAT3 vs H3K4me3) unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,3,5,8]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[5]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[8]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,3]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,3,5,8]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,5,8]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[8]}],"complexes":[],"partners":["SOX2","TET1","EP300","PCGF3","PCGF5","RELA","STAT3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NXF1","full_name":"Testis-expressed protein 10","aliases":[],"length_aa":929,"mass_kda":105.7,"function":"Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211)","subcellular_location":"Nucleus, nucleoplasm; Cytoplasm; Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9NXF1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TEX10","classification":"Common Essential","n_dependent_lines":1024,"n_total_lines":1208,"dependency_fraction":0.847682119205298},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DRG1","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2},{"gene":"RACK1","stoichiometry":0.2},{"gene":"RBM42","stoichiometry":0.2},{"gene":"RBM8A","stoichiometry":0.2},{"gene":"SRP19","stoichiometry":0.2},{"gene":"SRP72","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TEX10","total_profiled":1310},"omim":[{"mim_id":"616717","title":"TESTIS-EXPRESSED GENE 10; TEX10","url":"https://www.omim.org/entry/616717"},{"mim_id":"609455","title":"PROLINE-, GLUTAMIC ACID-, AND LEUCINE-RICH PROTEIN 1; PELP1","url":"https://www.omim.org/entry/609455"},{"mim_id":"300964","title":"LAS1-LIKE RIBOSOME BIOGENESIS FACTOR; LAS1L","url":"https://www.omim.org/entry/300964"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TEX10"},"hgnc":{"alias_symbol":["FLJ20287","bA208F1.2","Ipi1"],"prev_symbol":[]},"alphafold":{"accession":"Q9NXF1","domains":[{"cath_id":"-","chopping":"399-404_428-536","consensus_level":"medium","plddt":87.1275,"start":399,"end":536},{"cath_id":"-","chopping":"682-846","consensus_level":"high","plddt":87.9846,"start":682,"end":846},{"cath_id":"-","chopping":"859-929","consensus_level":"medium","plddt":74.4885,"start":859,"end":929}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXF1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXF1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXF1-F1-predicted_aligned_error_v6.png","plddt_mean":80.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TEX10","jax_strain_url":"https://www.jax.org/strain/search?query=TEX10"},"sequence":{"accession":"Q9NXF1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NXF1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NXF1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXF1"}},"corpus_meta":[{"pmid":"25936917","id":"PMC_25936917","title":"Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming.","date":"2015","source":"Cell stem cell","url":"https://pubmed.ncbi.nlm.nih.gov/25936917","citation_count":81,"is_preprint":false},{"pmid":"29054931","id":"PMC_29054931","title":"Polycomb group RING finger proteins 3/5 activate transcription via an interaction with the pluripotency factor Tex10 in embryonic stem cells.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29054931","citation_count":41,"is_preprint":false},{"pmid":"35219000","id":"PMC_35219000","title":"LINC00624/TEX10/NF-κB axis promotes proliferation and migration of human prostate cancer cells.","date":"2022","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/35219000","citation_count":32,"is_preprint":false},{"pmid":"39025062","id":"PMC_39025062","title":"E3 ubiquitin ligase IPI1 controls rice immunity and flowering via both E3 ligase-dependent and -independent pathways.","date":"2024","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/39025062","citation_count":26,"is_preprint":false},{"pmid":"30045663","id":"PMC_30045663","title":"Tex10 is upregulated and promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma.","date":"2018","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/30045663","citation_count":21,"is_preprint":false},{"pmid":"31638260","id":"PMC_31638260","title":"Tex10 promotes stemness and EMT phenotypes in esophageal squamous cell carcinoma via the Wnt/β‑catenin pathway.","date":"2019","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/31638260","citation_count":21,"is_preprint":false},{"pmid":"33760161","id":"PMC_33760161","title":"LncRNA GATA3‑AS1‑miR‑30b‑5p‑Tex10 axis modulates tumorigenesis in pancreatic cancer.","date":"2021","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/33760161","citation_count":21,"is_preprint":false},{"pmid":"32995120","id":"PMC_32995120","title":"RNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF-κB Activation.","date":"2020","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/32995120","citation_count":21,"is_preprint":false},{"pmid":"34966825","id":"PMC_34966825","title":"TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6.","date":"2021","source":"Journal of immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/34966825","citation_count":11,"is_preprint":false},{"pmid":"39988597","id":"PMC_39988597","title":"Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39988597","citation_count":7,"is_preprint":false},{"pmid":"37792308","id":"PMC_37792308","title":"Tex10 interacts with STAT3 to regulate hepatocellular carcinoma growth and metastasis.","date":"2023","source":"Molecular carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/37792308","citation_count":5,"is_preprint":false},{"pmid":"39863615","id":"PMC_39863615","title":"Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39863615","citation_count":5,"is_preprint":false},{"pmid":"26046753","id":"PMC_26046753","title":"Tex10: A New Player in the Core Pluripotency Circuitry.","date":"2015","source":"Cell stem cell","url":"https://pubmed.ncbi.nlm.nih.gov/26046753","citation_count":4,"is_preprint":false},{"pmid":"36865339","id":"PMC_36865339","title":"The pluripotency factor Tex10 finetunes Wnt signaling for PGC and male germline development.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36865339","citation_count":2,"is_preprint":false},{"pmid":"40330585","id":"PMC_40330585","title":"TEX10: A Novel Drug Target and Potential Therapeutic Direction for Sleep Apnea Syndrome.","date":"2025","source":"Nature and science of sleep","url":"https://pubmed.ncbi.nlm.nih.gov/40330585","citation_count":1,"is_preprint":false},{"pmid":"40086620","id":"PMC_40086620","title":"Regulatory role of TEX10 gene in proliferation differentiation and apoptosis of bovine myoblasts.","date":"2025","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/40086620","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9642,"output_tokens":2947,"usd":0.036566,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10369,"output_tokens":2926,"usd":0.062497,"stage2_stop_reason":"end_turn"},"total_usd":0.099063,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"Tex10 physically interacts with Sox2 (identified via a protein interaction network surrounding Sox2) and is enriched at super-enhancers in a Sox2-dependent manner in embryonic stem cells, where it coordinates histone acetylation and DNA demethylation at super-enhancers to sustain pluripotency.\",\n      \"method\": \"Protein interaction network/Co-IP, ChIP, bisulfite sequencing, loss-of-function (shRNA knockdown) with pluripotency and reprogramming phenotypic readouts\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, ChIP occupancy, DNA methylation assays, and functional rescue experiments across mouse and human cells in one focused study\",\n      \"pmids\": [\"25936917\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Tex10 coordinates with Tet1 and p300 at super-enhancers to regulate histone acetylation and DNA demethylation, functioning as a core component of the pluripotency epigenetic regulatory complex.\",\n      \"method\": \"Co-IP/pulldown, ChIP-seq, loss-of-function assays in ESCs\",\n      \"journal\": \"Cell stem cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ChIP-seq occupancy and Co-IP identifying complex components, multiple orthogonal methods in single focused study\",\n      \"pmids\": [\"25936917\", \"26046753\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Tex10 physically interacts with Pcgf3 and Pcgf5 (polycomb group RING finger proteins) and with the transcriptional co-activator p300 in embryonic stem cells; Pcgf3/5 deletion substantially reduces Tex10 and p300 occupancy at target gene promoters, indicating Tex10 is recruited to these loci through Pcgf3/5.\",\n      \"method\": \"Proteomic/mass spectrometry interactome, Co-IP, ChIP-seq, CRISPR-Cas9 deletion of Pcgf3/5 with RNA-seq phenotypic readout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — proteomic interactome plus Co-IP plus ChIP occupancy studies with genetic loss-of-function, multiple orthogonal methods\",\n      \"pmids\": [\"29054931\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TEX10 interacts with RELA (NF-κB subunit), increases its nuclear localization, and promotes RELA occupancy at target gene promoters (including TNFAIP8, SAT1, and IL6ST), thereby promoting colorectal cancer cell proliferation in an RELA-dependent manner.\",\n      \"method\": \"shRNA library screen, Co-IP, nuclear fractionation, ChIP, gene set enrichment analysis, in vitro and in vivo proliferation assays\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP of interaction, ChIP showing RELA promoter occupancy, nuclear localization assay, and functional rescue/KD with defined molecular readouts in single study\",\n      \"pmids\": [\"32995120\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TEX10 knockdown in hepatocellular carcinoma cells decreases expression of stem cell markers and drug resistance, and TEX10 promotes cancer stemness through activation of the STAT3 signaling pathway.\",\n      \"method\": \"shRNA knockdown, Western blot, RT-qPCR, sphere formation, drug resistance assays with STAT3 pathway readouts\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — loss-of-function with pathway readout, but mechanistic link to STAT3 is based on downstream marker analysis without direct interaction data in this paper\",\n      \"pmids\": [\"30045663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TEX10 physically interacts with STAT3 (shown by Co-IP) and promotes p300-mediated STAT3 acetylation; p300 silencing abolishes TEX10-enhanced STAT3 transcriptional activity, establishing a TEX10–p300–STAT3 axis controlling HCC invasion and EMT.\",\n      \"method\": \"Co-immunoprecipitation, dual-luciferase reporter assay, ChIP, immunofluorescence, p300 siRNA silencing, transwell and xenograft assays\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, ChIP, reporter assay, and p300 rescue experiment provide multiple orthogonal methods supporting the mechanism in a single focused study\",\n      \"pmids\": [\"37792308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TEX10 knockdown in esophageal squamous cell carcinoma cells inhibits proliferation, induces apoptosis and cell cycle arrest, reduces stemness and invasiveness, and suppresses EMT via inhibition of Wnt/β-catenin signaling.\",\n      \"method\": \"Lentiviral shRNA knockdown, CCK-8 proliferation assay, flow cytometry (apoptosis/cell cycle), Transwell assay, sphere formation, Western blot for β-catenin pathway components\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — loss-of-function with pathway readouts, but mechanistic link to Wnt/β-catenin is based on downstream marker changes without direct interaction or ChIP data\",\n      \"pmids\": [\"31638260\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TEX10 stabilizes XRCC6 protein (Ku70) and thereby controls Wnt/β-catenin signaling and DNA repair pathways in bladder carcinoma; TEX10 knockout reduces radiotherapy resistance.\",\n      \"method\": \"Gene knockout, Western blot for XRCC6, in vitro and in vivo proliferation/metastasis assays, radiotherapy resistance assay\",\n      \"journal\": \"Journal of immunology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, mechanism of TEX10–XRCC6 stabilization inferred without direct interaction data (no Co-IP or pulldown described in abstract)\",\n      \"pmids\": [\"34966825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Tex10 binds to H3K4me3-marked promoters of Psmd3 and Psmd7 (negative regulators of Wnt signaling) and activates their expression, thereby restraining Wnt signaling during spermatogenesis and ESC-to-PGCLC differentiation; Tex10-null spermatocytes arrest at metaphase I, compromising round spermatid formation.\",\n      \"method\": \"Conditional knockout mouse model, dTAG-degron ESCs, bulk and single-cell RNA-seq, chromatin occupancy (ChIP or CUT&RUN), ESC-to-PGCLC differentiation assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO in vivo, chromatin occupancy at specific loci, single-cell transcriptomics, and functional differentiation assay with overexpression rescue; multiple orthogonal methods and replicated in peer-reviewed publication\",\n      \"pmids\": [\"39988597\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Tex10 binds Wnt negative regulator gene promoters marked by H3K4me3 at the PGCLC stage, and depletion or overexpression of Tex10 hyperactivates or attenuates Wnt signaling, respectively, resulting in compromised or enhanced PGCLC specification efficiency.\",\n      \"method\": \"Chromatin occupancy (ChIP), Tex10 conditional KO mice, single-cell RNA-seq, ESC-to-PGCLC differentiation assay, overexpression\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and genetic loss/gain-of-function with functional readout, but preprint status and overlap with published version (PMID 39988597) lower confidence\",\n      \"pmids\": [\"36865339\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"LINC00624 and TEX10 form a co-regulatory axis that stimulates NF-κB activity to promote proliferation and migration of prostate cancer cells.\",\n      \"method\": \"In vitro knockdown assays, in vivo xenograft, NF-κB reporter/activity assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-regulatory axis described but molecular mechanism between LINC00624 and TEX10 not detailed in abstract; single lab, limited mechanistic depth\",\n      \"pmids\": [\"35219000\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEX10 promotes expression of cell cycle regulators CDK2 and PCNA, increases S-phase entry, enhances differentiation marker genes MYOG and MYOD, and inhibits apoptosis in bovine myoblasts, with transcriptomic analysis implicating PI3K-Akt, cAMP, and IL-17 signaling pathways.\",\n      \"method\": \"CCK-8, EdU incorporation, qPCR, Western blot, immunofluorescence, flow cytometry (cell cycle), overexpression and knockdown, transcriptomic analysis\",\n      \"journal\": \"The international journal of biochemistry & cell biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single study in bovine cells, pathway involvement inferred from transcriptomics without direct mechanistic interrogation of pathway components\",\n      \"pmids\": [\"40086620\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TEX10 is a transcriptional co-regulator that functions as a core component of the pluripotency network by physically associating with Sox2, Tet1, p300, and Pcgf3/5 to coordinate histone acetylation and DNA demethylation at super-enhancers in embryonic stem cells; in somatic and cancer contexts it activates NF-κB/RELA nuclear localization and STAT3 transcriptional activity (via p300-mediated STAT3 acetylation), while in germ cell development it binds H3K4me3-marked promoters of Wnt negative regulators (Psmd3/Psmd7) to restrain Wnt signaling and thereby enable spermatogenesis and primordial germ cell specification.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TEX10 is a chromatin-associated transcriptional co-regulator that operates within the embryonic stem cell pluripotency network and is repurposed as a transcriptional effector in germ cell development and cancer [#0, #8]. In embryonic stem cells it is identified through the Sox2 protein interaction network and is recruited to super-enhancers in a Sox2-dependent manner, where it acts together with Tet1 and the histone acetyltransferase p300 to coordinate histone acetylation and DNA demethylation that sustain pluripotency [#0, #1]. Its occupancy at target promoters is directed by the polycomb group RING finger proteins Pcgf3 and Pcgf5, whose deletion sharply reduces both TEX10 and p300 chromatin binding [#2]. In germ cell development, Tex10 binds H3K4me3-marked promoters of the Wnt negative regulators Psmd3 and Psmd7 to activate their expression and thereby restrain Wnt signaling; its loss arrests spermatocytes at metaphase I and impairs primordial germ cell-like cell specification [#8]. In cancer contexts TEX10 functions as a transcriptional amplifier: it physically interacts with the NF-\\u03baB subunit RELA to increase its nuclear localization and promoter occupancy in colorectal cancer [#3], and it binds STAT3 to promote p300-mediated STAT3 acetylation and transcriptional activity driving hepatocellular carcinoma invasion [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Establishing that TEX10 is a functional node of the pluripotency network answered whether it had a defined molecular role, placing it on Sox2-dependent super-enhancers controlling chromatin state.\",\n      \"evidence\": \"Sox2 interaction network with Co-IP, ChIP, bisulfite sequencing, and shRNA loss-of-function in mouse and human ESCs\",\n      \"pmids\": [\"25936917\", \"26046753\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct catalytic activity of TEX10 itself not defined; it appears to act as a scaffold/recruiter rather than an enzyme\", \"Whether super-enhancer recruitment requires Sox2 binding directly or an intermediary not resolved here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identifying Pcgf3/5 as recruiters answered how TEX10 and p300 reach target promoters, linking a polycomb-associated module to TEX10 chromatin localization.\",\n      \"evidence\": \"Mass-spectrometry interactome, Co-IP, ChIP-seq, and CRISPR-Cas9 deletion of Pcgf3/5 with RNA-seq in ESCs\",\n      \"pmids\": [\"29054931\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the TEX10\\u2013Pcgf3/5 interaction unknown\", \"Whether the same recruitment logic applies outside ESCs not tested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linking TEX10 to cancer stemness extended its role beyond ESCs, implicating STAT3 signaling in hepatocellular carcinoma.\",\n      \"evidence\": \"shRNA knockdown with stem-cell marker, drug resistance, and STAT3 pathway readouts\",\n      \"pmids\": [\"30045663\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"STAT3 link inferred from downstream markers without direct interaction data in this study\", \"No chromatin occupancy data linking TEX10 to STAT3 targets\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connecting TEX10 to Wnt/\\u03b2-catenin signaling in esophageal carcinoma broadened its pathway repertoire, presaging the Wnt-regulatory role later defined mechanistically in germ cells.\",\n      \"evidence\": \"Lentiviral shRNA knockdown with proliferation, apoptosis, EMT, and \\u03b2-catenin Western blot readouts\",\n      \"pmids\": [\"31638260\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link to Wnt based on downstream markers without interaction or ChIP data\", \"Directionality (TEX10 promotes vs. restrains Wnt) differs from germ cell findings, unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrating a TEX10\\u2013RELA interaction answered how TEX10 couples to inflammatory transcription, showing it drives NF-\\u03baB nuclear localization and target occupancy in colorectal cancer.\",\n      \"evidence\": \"shRNA screen, Co-IP, nuclear fractionation, ChIP, and in vitro/in vivo proliferation assays\",\n      \"pmids\": [\"32995120\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How TEX10 increases RELA nuclear import mechanistically not defined\", \"Whether p300 participates in this axis as it does for STAT3 not tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defining the TEX10\\u2013p300\\u2013STAT3 axis provided the direct molecular mechanism behind earlier STAT3 association, showing TEX10 promotes p300-mediated STAT3 acetylation.\",\n      \"evidence\": \"Reciprocal Co-IP, dual-luciferase reporter, ChIP, p300 siRNA rescue, transwell and xenograft assays\",\n      \"pmids\": [\"37792308\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether TEX10 directly bridges p300 and STAT3 or acts indirectly not structurally resolved\", \"Relationship between this acetylation function and the ESC p300 module unexplored\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Conditional knockout established TEX10's physiological function in germ cell development, showing it activates Psmd3/Psmd7 at H3K4me3 promoters to restrain Wnt and enable spermatogenesis.\",\n      \"evidence\": \"Conditional KO mice, dTAG-degron ESCs, bulk/single-cell RNA-seq, chromatin occupancy, and PGCLC differentiation with rescue\",\n      \"pmids\": [\"39988597\", \"36865339\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How TEX10 reads or is recruited to H3K4me3-marked promoters not defined\", \"Reconciliation of Wnt-restraining (germ cells) versus Wnt-promoting (cancer) roles unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic biochemical activity of TEX10 — whether it possesses any catalytic function or acts purely as a scaffold/recruiter — remains undefined across all contexts.\",\n      \"evidence\": \"No discovery in the timeline assigns TEX10 a direct enzymatic activity\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of TEX10 or its complexes\", \"Mechanism of context-dependent partner selection (Pcgf3/5 vs RELA vs STAT3 vs H3K4me3) unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 3, 5, 8]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 3, 5, 8]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 5, 8]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SOX2\", \"TET1\", \"EP300\", \"PCGF3\", \"PCGF5\", \"RELA\", \"STAT3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}