An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.
An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.
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一份完整的人类胎盘发育图谱描绘了滋养层干细胞的基本调节因子。
DOI：
10.1242/dev.200171
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发表时间：
2022-07-01
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影响因子：
--
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中科院分区：
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--
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滋养层谱系通过介导胚胎植入、免疫耐受、营养供应和气体交换来保障胎儿发育。人类滋养层干细胞（hTSC）提供了研究胎盘组织谱系规范的平台；然而，控制自我更新的监管网络仍然难以捉摸。在这里，我们展示了人类滋养层从受精卵到妊娠中期发育的单细胞图谱以及 hTSC 的单细胞分析。我们确定了体内滋养层谱系的转录网络，并利用概率模型来确定 MAPK 信号在滋养层分化中的作用。胎盘和胚泡来源的 hTSC 始终映射于晚期滋养外胚层和早期细胞滋养层之间，而胚泡滋养层则对应于滋养外胚层。我们在功能上评估了 siRNA 筛选中预测的细胞滋养层网络的需求，并揭示了 hTSC 自我更新的 15 个重要调节因子，包括 MAZ、NFE2L3、TFAP2C、NR2F2 和 CTNNB1。我们的人类滋养层图谱提供了强大的分析资源，可描述滋养层细胞的命运获取、阐明 hTSC 自我更新所需的转录因子以及衡量体外培养细胞的发育阶段。摘要：人类滋养层从受精卵到妊娠中期发育的连续伪时间轨迹决定了体外滋养层培养物的体内对应物，并确定了人类滋养层干细胞自我更新的关键调节因子。
The trophoblast lineage safeguards fetal development by mediating embryo implantation, immune tolerance, nutritional supply and gas exchange. Human trophoblast stem cells (hTSCs) provide a platform to study lineage specification of placental tissues; however, the regulatory network controlling self-renewal remains elusive. Here, we present a single-cell atlas of human trophoblast development from zygote to mid-gestation together with single-cell profiling of hTSCs. We determine the transcriptional networks of trophoblast lineages in vivo and leverage probabilistic modelling to identify a role for MAPK signalling in trophoblast differentiation. Placenta- and blastoid-derived hTSCs consistently map between late trophectoderm and early cytotrophoblast, in contrast to blastoid-trophoblast, which correspond to trophectoderm. We functionally assess the requirement of the predicted cytotrophoblast network in an siRNA-screen and reveal 15 essential regulators for hTSC self-renewal, including MAZ, NFE2L3, TFAP2C, NR2F2 and CTNNB1. Our human trophoblast atlas provides a powerful analytical resource to delineate trophoblast cell fate acquisition, to elucidate transcription factors required for hTSC self-renewal and to gauge the developmental stage of in vitro cultured cells. Summary: A continuous pseudotime trajectory of human trophoblast development from zygote to mid-gestation determines the in vivo counterpart of in vitro trophoblast cultures and identifies key regulators of human trophoblast stem cell self renewal.
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影响因子：
12.3
作者：
Boukouvalas A;Hensman J;Rattray M
通讯作者：
Rattray M
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13.3
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Theunissen, Thorold W.
影响因子：
3.8
作者：
Enders, AC;Blankenship, TN;Jones, CJP
通讯作者：
Jones, CJP
影响因子：
5.8
作者：
Angerer, Philipp;Haghverdi, Laleh;Buettner, Florian
通讯作者：
Buettner, Florian