Kalkan Tüzer, Olova Nelly, Roode Mila, Mulas Carla, Lee Heather J, Nett Isabelle, Marks Hendrik, Walker Rachael, Stunnenberg Hendrik G, Lilley Kathryn S, Nichols Jennifer, Reik Wolf, Bertone Paul, Smith Austin
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK
Babraham Institute, Cambridge CB22 3AT, UK.
Development. 2017 Apr 1;144(7):1221-1234. doi: 10.1242/dev.142711. Epub 2017 Feb 7.
Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naïve pluripotency. Here, we examine the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life reporter to isolate cells either side of exit from naïve status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state display features of early post-implantation epiblast and are distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naïve cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.
小鼠胚胎干细胞通过屏蔽诱导信号而被锁定在自我更新状态。在最小条件下从这种基础状态释放，提供了一个用于描绘从原始多能性发育进程的系统。在这里，我们研究初始转变过程。胚胎干细胞群体表现出异步性。因此，我们利用一个半衰期短的报告基因来分离处于从原始状态退出前后的细胞。单细胞中胚胎干细胞身份的消失是急剧的。它仅在原始多能性因子几乎完全消除后发生，但在谱系特异性标记物出现之前。刚从胚胎干细胞状态脱离的细胞表现出植入后早期上胚层的特征，并且与始发态上胚层不同。它们还表现出全基因组DNA甲基化增加，处于早期和晚期上胚层之间的中间状态。这些发现与原始细胞向多能性的一个独特的形成阶段转变以准备谱系始发的观点一致。
