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.

中文翻译：

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转录因子共表达介导胚胎和胚胎外分化的谱系启动

在早期哺乳动物发育中，卵裂期卵裂球和内细胞团（ICM）细胞共同表达胚胎和胚胎外转录决定簇。使用基于蛋白质的双报告基因，我们鉴定了一个胚胎干细胞（ESC）群体，它与胚胎因子 SOX2 共同表达胚胎外因子 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力，同时保持外胚层能力。为了将这些细胞中的转录因子结合与未来的命运联系起来，我们描述了 ESC 和幼稚胚胎外内胚层干细胞中的完整增强子集，并评估了 ICM 样 ESC 亚群中这些元件的 SOX2 和 GATA6 结合。这两个因子都支持这些谱系中的协同识别，GATA6 与 SOX2 结合在一部分多能性增强子上，而 SOX2 与 GATA6 更广泛地在内胚层增强子上结合，表明这些拮抗因子之间的协同结合既支持自我更新，又为祖细胞以后的分化做好准备。 。