Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome
Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome
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DOI：
10.1016/j.stemcr.2020.06.003
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发表时间：
2020-07-14
影响因子：
5.9
通讯作者：
Pastor, William A.
中科院分区：
文献类型：
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作者：
Cinkornpumin, Jessica K.;Kwon, Sin Young;Pastor, William A.
人类胚胎干细胞(HESCs)很容易分化为体细胞或生殖系，但形成胎盘或卵黄囊等胚胎外系的能力受到损害。在这里，我们证明了幼稚的hESCs可以转化为表现出人类滋养层干细胞(HTSCs)的细胞和分子表型，这些细胞和分子表型来自于人胎盘或胚泡。转分化的hTSCs表现出核心胎盘基因的重新激活，获得类似胎盘的甲基组，以及向绒毛外滋养细胞和合体滋养细胞分化的能力。在转分化的hTSCs和胎盘hTSCs之间观察到微小的差异，最显著的是在某些印记基因的表达上。这些结果表明，幼稚的hESCs可以分化为胚外血统，并展示了一种模拟人类滋养层规范和胎盘甲基组建立的新方法。
Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here, we demonstrate that naive hESCs can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting "transdifferentiated'' hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results suggest that naive hESCs can differentiate to extra-embryonic lineage and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.