Capturing human trophoblast development with naive pluripotent stem cells in vitro
Capturing human trophoblast development with naive pluripotent stem cells in vitro
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DOI：
10.1016/j.stem.2021.03.013
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发表时间：
2021-06-03
期刊：
影响因子：
23.9
通讯作者：
Takashima, Yasuhiro
中科院分区：
文献类型：
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作者：
Io, Shingo;Kabata, Mio;Takashima, Yasuhiro
滋养层细胞是维持妊娠所必需的胚外细胞。人的滋养层细胞由桑椹胚层分化为滋养层(TE)，植入后分化为细胞滋养层(CTs)、合体滋养层细胞(STS)和绒毛外滋养层细胞(EVTs)，构成胎盘。在这里，我们展示了天真的，但没有启动的，人类多能干细胞(PSCs)概括了滋养层的发育。朴素的PSC衍生的TE和CTs(NCTs)重建了人和猴子的TE到CT的转变。神经干细胞可自我更新为CT干细胞，具有绒毛状CTs和早孕期CTs在细胞柱中增殖的特征。值得注意的是，尽管PSCs分化为滋养细胞样细胞(BMP4、A83-01和PD173074[BAP]处理的PSCs[pBAP])，但pBAPs不同于nCTs和人胎盘附着的CT干细胞，表现出与羊膜一致的特性。我们的发现为人类滋养层细胞的发育建立了一个真实的范例，展示了幼稚的人类PSCs的宝贵特性。我们的系统为研究滋养细胞发育和相关疾病的分子机制提供了一个平台。
Trophoblasts are extraembryonic cells that are essential for maintaining pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs), composing the placenta. Here we show that naive, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naive PSC-derived TE and CTs (nCTs) recreated human and monkey TE-to-CT transition. nCTs self-renewed as CT stem cells and had the characteristics of proliferating villous CTs and CTs in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (BMP4, A83-01, and PD173074 [BAP]-treated primed PSCs [pBAPs]), pBAPs were distinct from nCTs and human placentaderived CT stem cells, exhibiting properties consistent with the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naive human PSCs. Our system provides a platform to study the molecular mechanisms underlying trophoblast development and related diseases.