Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses.
Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses.
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通过单细胞转录组和功能分析剖析人胚胎骨骼干细胞个体发育
DOI：
10.1038/s41422-021-00467-z
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发表时间：
2021-07
期刊：
影响因子：
44.1
通讯作者：
Yue R
中科院分区：
文献类型：
--
作者：
He J;Yan J;Wang J;Zhao L;Xin Q;Zeng Y;Sun Y;Zhang H;Bai Z;Li Z;Ni Y;Gong Y;Li Y;He H;Bian Z;Lan Y;Ma C;Bian L;Zhu H;Liu B;Yue R
人类骨骼干细胞（SSC）已在胎儿和成人长骨中发现。然而，在早期骨骼发育过程中，人胚胎精原干细胞的时空个体发育仍然难以捉摸。在这里，我们绘制了人类肢芽和胚胎长骨的转录景观，以单细胞分辨率来解决这个基本问题。我们发现显着的异质性在人类肢芽间充质和上皮细胞，并对齐他们沿着近端-远端和前后轴使用已知的标记基因。骨软骨形成祖细胞首先出现在核心肢芽间充质中，其在经历软骨内骨化的胚胎长骨中产生多个干/祖细胞群体。重要的是，软骨膜胚胎骨骼干/祖细胞（eSSPC）的子集被确定，它可以自我更新，并产生骨软骨谱系细胞，但不是脂肪细胞或造血基质。eSSPCs由粘附分子CADM 1标记，并高度富集FOXP 1/2转录网络。有趣的是，在人胚胎颅骨矢状缝中也发现了具有相似表型标记和转录网络的神经嵴源性细胞。总之，这项研究揭示了人类胚胎骨骼发生过程中的细胞异质性和谱系层次，并确定了不同的骨骼干/祖细胞，协调软骨内和膜内骨化。
Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal–distal and anterior–posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1073/pnas.1808790115
发表时间：
2018-11-13
影响因子：
11.1
作者：
Bausch-Fluck D;Goldmann U;Müller S;van Oostrum M;Müller M;Schubert OT;Wollscheid B
通讯作者：
Wollscheid B
影响因子：
64.5
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
11.8
作者：
Bialek, P;Kern, B;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
64.8
作者：
Chan, Charles K. F.;Chen, Ching-Cheng;Luppen, Cynthia A.;Kim, Jae-Beom;DeBoer, Anthony T.;Wei, Kevin;Helms, Jill A.;Kuo, Calvin J.;Kraft, Daniel L.;Weissman, Irving L.
通讯作者：
Weissman, Irving L.