reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
Stem Cell Reports. 2024 Feb 13;19(2):174-186. doi: 10.1016/j.stemcr.2023.12.002. Epub 2024 Jan 11.
In early mammalian development, cleavage stage blastomeres and inner cell mass (ICM) cells co-express embryonic and extra-embryonic transcriptional determinants. Using a protein-based double reporter we identify an embryonic stem cell (ESC) population that co-expresses the extra-embryonic factor GATA6 alongside the embryonic factor SOX2. Based on single cell transcriptomics, we find this population resembles the unsegregated ICM, exhibiting enhanced differentiation potential for endoderm while maintaining epiblast competence. To relate transcription factor binding in these cells to future fate, we describe a complete enhancer set in both ESCs and naive extra-embryonic endoderm stem cells and assess SOX2 and GATA6 binding at these elements in the ICM-like ESC sub-population. Both factors support cooperative recognition in these lineages, with GATA6 bound alongside SOX2 on a fraction of pluripotency enhancers and SOX2 alongside GATA6 more extensively on endoderm enhancers, suggesting that cooperative binding between these antagonistic factors both supports self-renewal and prepares progenitor cells for later differentiation.
在早期哺乳动物发育过程中，卵裂期的胚胎细胞和内细胞团（ICM）细胞共同表达胚胎和胚胎外转录决定因素。我们使用基于蛋白质的双报告基因，鉴定出一个胚胎干细胞（ESC）群体，该群体同时表达胚胎因子 SOX2 和胚胎外因子 GATA6。基于单细胞转录组学，我们发现该群体类似于未分离的 ICM，表现出增强的内胚层分化潜能，同时保持胚胎外胚层的能力。为了将这些细胞中的转录因子结合与未来命运联系起来，我们描述了 ESC 和原始胚胎外胚层干细胞中的完整增强子集，并评估了 SOX2 和 GATA6 在 ICM 样 ESC 亚群中这些元件上的结合。这两种因子都支持在这些谱系中的合作识别，GATA6 与 SOX2 共同结合在一部分多能性增强子上，而 SOX2 与 GATA6 更广泛地结合在内胚层增强子上，这表明这些拮抗因子之间的合作结合既支持自我更新，又为祖细胞的后续分化做好准备。
