Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states.
Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states.
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DOI：
10.1016/j.stem.2008.07.027
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发表时间：
2008-10-09
期刊：
影响因子：
23.9
通讯作者：
Surani MA
中科院分区：
文献类型：
--
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
胚胎干细胞（ESC）显然是均匀的自我更新细胞，但是Stella是植入前胚胎和生殖细胞的标记，在ESC中显示出异质的表达。在这里，我们表明Stella阳性ESC像内部细胞质量（ICM）一样，而Stella阴性细胞就像层细胞，尽管这些种群表现出互换性，反映了对固有程序的依从性。因此，ESC处于亚稳态状态，因为它们在ICM-和epiblast样表型之间转移，这提供了对其不稳定性，可塑性和多能性的见解。这种平衡是通过环境和表观遗传提示可逆的。例如，馈线细胞的缺失导致向层状状态转移，而trichostatin a（组蛋白的抑制剂deactelylase的抑制剂）恢复了Stella阳性群体。一致地，这两个种群显示出不同的组蛋白修饰，但在Stella基因座中具有低甲基化的DNA，并在引起分化时具有功能差异。 Stella阴性细胞显然更像是植入后培养细胞衍生的干细胞（EPISC），但斯特拉基因座在后者中被过度甲基化和抑制，这表示ESC和Episcs之间的强大边界。
Embryonic stem cells (ESC) are apparently homogeneous self-renewing cells, but Stella, a marker of preimplantation embryos and germ cells showed heterogeneous expression in ESCs. Here we show that the Stella-positive ESCs were like the inner cell mass (ICM) while the Stella-negative cells were like the epiblast cells, although these populations exhibited interchangeability that reflected an adherence to an inherent program. Thus, ESCs are in a metastable state since they shift between the ICM- and epiblast-like phenotypes, which provides an insight into their instability, plasticity and pluripotency. This equilibrium was skewed reversibly by environmental and epigenetic cues; for example, the absence of signals from feeder cells caused a shift towards an epiblast-like state while trichostatin A, an inhibitor of histone deactelylase, restored Stella-positive population. Consistently, the two populations showed different histone modifications but with hypomethylated DNA in stella locus, as well as functional differences when induced to undergo differentiation. The Stella-negative cells were apparently more like the post-implantation epiblast-derived stem cells (EpiSCs), except that the stella locus was hypermethylated and repressed in the latter, which denotes a robust boundary between ESCs and EpiSCs.
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