Derivation of trophoblast stem cells from naive human pluripotent stem cells
Derivation of trophoblast stem cells from naive human pluripotent stem cells
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DOI：
10.7554/elife.52504
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发表时间：
2020-02-12
期刊：
影响因子：
7.7
通讯作者：
Theunissen, Thorold W.
中科院分区：
文献类型：
--
作者：
Dong, Chen;Beltcheva, Mariana;Theunissen, Thorold W.
幼稚的人类多能干细胞（hPSC）提供了在植入前发育期间决定细胞命运的独特实验平台，但其谱系潜力仍不完全表征。由于幼稚hPSC与滋养层细胞共享转录和表观基因组特征，因此已经提出幼稚状态可能具有增强的沿该胚外谱系分化的倾向沿着。在这里，我们检查了同基因幼稚和致敏的hPSC的滋养层潜能。我们发现幼稚hPSC可以直接产生人滋养层干细胞（hTSCs）并经历进一步分化为绒毛外滋养层和合体滋养层。相反，引发的hPSC不支持hTSC衍生，但响应于BMP 4产生非自我更新的细胞滋养层。全局转录组和染色质可及性分析表明，来源于幼稚hPSC的hTSC与胚泡来源的hTSC相似，并获得植入后滋养外胚层的特征。从幼稚hPSC衍生hTSC将能够阐明控制正常人滋养层发育和相关病理的早期机制。
Naive human pluripotent stem cells (hPSCs) provide a unique experimental platform of cell fate decisions during pre-implantation development, but their lineage potential remains incompletely characterized. As naive hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the naive state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined the trophoblast potential of isogenic naive and primed hPSCs. We found that naive hPSCs can directly give rise to human trophoblast stem cells (hTSCs) and undergo further differentiation into both extravillous and syncytiotrophoblast. In contrast, primed hPSCs do not support hTSC derivation, but give rise to non-self-renewing cytotrophoblasts in response to BMP4. Global transcriptome and chromatin accessibility analyses indicate that hTSCs derived from naive hPSCs are similar to blastocyst-derived hTSCs and acquire features of post-implantation trophectoderm. The derivation of hTSCs from naive hPSCs will enable elucidation of early mechanisms that govern normal human trophoblast development and associated pathologies.