Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency - PubMed (nih.gov)
摘要
Pluripotent cells emerge as a naive founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs) represent the initial naive and final primed phases of pluripotency, respectively. Here, we investigate the intermediate formative stage. Using minimal exposure to specification cues, we derive stem cells from formative mouse epiblast. Unlike ESCs or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonize somatic tissues and germline in chimeras. Whole-transcriptome analyses show similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells show distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naive cells or embryos support expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.
多能细胞在胚泡中作为naive的创始群体出现，获得种系和体细胞形成的能力，然后进行谱系启动。小鼠胚胎干细胞 (ESCs) 和上胚层衍生干细胞 (EpiSCs) 分别代表多能性的初始naive期和最终primed期。在这里，我们研究了中间formative阶段。使用最少的分化诱导信号，我们从formative小鼠上胚层中提取干细胞。与 ESC 或 EpiSC 不同，formative stem (FS) 细胞直接响应生殖细胞诱导信号。它们在嵌合体中定殖体细胞组织和种系。全转录组分析显示与原肠胚形成前的上胚层相似。信号响应性和染色质可及性特征反映了谱系获能。此外，FS 细胞表现出明显的转录因子依赖性，严重依赖 Otx2。最后，应用于人类naive细胞或胚胎的 FS 细胞培养条件支持相似干细胞的扩增，这与哺乳动物多能性轨迹上的保守阶段一致。
笔记
