ArticleEMBO reports2026
Nanog mediated control of TBX3-GATA6 circuitry in primitive endoderm differentiation of mESCs.
Hao Wu, Ying Ye, Hongxia Dai, Peixin Chen, Tenghui Yang, Zhifang Li, Li Li, Chirag Parsania, Junjun Ding, Man Zhang and 5 more
Abstract read
In one paragraphArticle in EMBO reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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15 authors.
Hao Wu *Cam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
Ying Ye *Department of Clinical Pathobiology and Immunological Testing, School of Medical Laboratory, Qilu Medical University, 255300, Zibo, China. yeying@qlmu.edu.cn.ORCID 0009-0000-3435-0656 Peixin ChenCam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
Tenghui YangCam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
Zhifang LiShenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.ORCID 0009-0000-7752-2454 Li LiCollege of Life Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, 430070, Wuhan, China.ORCID 0000-0002-7656-7957 Chirag ParsaniaGene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Sydney, NSW, Australia.
Junjun DingRNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Man ZhangGuangzhou National Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, 510005, Guangzhou, Guangdong Province, China.
Erwei ZuoShenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.ORCID 0000-0001-8259-0275 Ulf SchmitzDepartment of Biomedical Sciences and Molecular and Cell Biology, College of Public Health, Medical, and Veterinary Sciences, James Cook University, Townsville, QLD, Australia.
Xi ChenShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China. chenx9@sustech.edu.cn.ORCID 0000-0003-2648-3146 Zhexin ZhuInstitute of Health and Medicine, Hefei comprehensive national science center, 4090 Guanhai Road, Heifei, China. zxzhu@ihm.ac.cn.ORCID 0000-0002-6864-4780 Wensheng ZhangCam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China. zhangwensheng@suda.edu.cn.ORCID 0000-0002-6876-3173 Funding
Ministry of Science and Technology of the People's Republic of China (MOST) 2022YFA1104300MOST | National Natural Science Foundation of China (NSFC) 31970812MOST | National Natural Science Foundation of China (NSFC) 32170797MOST | National Natural Science Foundation of China (NSFC) 32470842
6 · The paper itselfAbstract
Cell fate decisions in the early embryo rely on reciprocal transcriptional networks that balance pluripotency with lineage commitment. NANOG is essential for directing the epiblast-primitive endoderm (PrE) fate choice, but the molecular mechanisms underlying its repressive activity remain incompletely understood. Here we show that NANOG partners with TBX3 and the PRC2 complex to maintain embryonic stem cell (ESC) identity by silencing PrE genes through newly identified distal enhancers. Loss of Nanog reduces PRC2-mediated repression of Gata6, initiating its expression independently of TBX3. Subsequent TBX3 upregulation enables its association with GATA6, driving a feed-forward programme that activates Gata6, Gata4 and Sox17 and promotes PrE differentiation. Thus, NANOG suppresses PrE fate not only by direct repression but also by preventing TBX3 from switching partners. These findings define a Nanog-Tbx3-Gata6 regulatory axis that integrates enhancer control, chromatin regulation and transcription factor redeployment to couple ESC maintenance with lineage commitment.
Indexed as
Cell DifferentiationEmbryonic Stem CellsEndodermGATA6 Transcription FactorHomeodomain ProteinsNanog Homeobox ProteinT-Box Domain ProteinsAnimalsCell LineageEnhancer Elements, GeneticGATA4 Transcription FactorGene Expression Regulation, DevelopmentalHMGB ProteinsMicePolycomb Repressive Complex 2Protein BindingGata4 protein, mouseGATA4 Transcription FactorGata6 protein, mouseGATA6 Transcription FactorHMGB ProteinsHomeodomain ProteinsNanog Homeobox ProteinNanog protein, mousePolycomb Repressive Complex 2Sox17 protein, mouseSOXF Transcription FactorsT-Box Domain ProteinsTbx3 protein, mouseEmbryonic Stem CellsNanogPRC2 ComplexPrimitive Endoderm
Identifiers
PMID41629627
PMCPMC12979688
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