祖细胞
生物
干细胞
细胞生物学
人口
细胞分化
计算生物学
再生(生物学)
遗传学
医学
基因
环境卫生
作者
Zi Yin,Junxin Lin,Ruojin Yan,Richun Liu,Mengfei Liu,Bo Zhou,Wenyan Zhou,Chengrui An,Yangwu Chen,Yin Hu,Chunmei Fan,Kun Zhao,Bingbing Wu,Xiaohui Zou,Hua Yu,Ahmed El-Hashash,Xiao Chen,Hongwei Ouyang
标识
DOI:10.1002/advs.202000938
摘要
Although being of utmost importance for human health and mobility, stem cell identity and hierarchical organization of musculoskeletal progenitors remain largely unexplored. Here, cells from E10.5, E12.5, and E15.5 murine limbs are analyzed by high throughput single-cell RNA sequencing to illustrate the cellular architecture during limb development. Single-cell transcriptional profiling demonstrates the identity and differentiation architecture of musculoskeletal stem cells (MSSC), soft and hard tissue progenitors through expression pattern of musculoskeletal markers (scleraxis [Scx], Hoxd13, Sox9, and Col1a1). This is confirmed by genetic in vivo lineage tracing. Moreover, single-cell analyses of Scx knockout mice tissues illustrates that Scx regulates MSSC self-renewal and proliferation potential. A high-throughput and low-cost multi-tissues RNA sequencing strategy further provides evidence that musculoskeletal system tissues, including muscle, bone, meniscus, and cartilage, are all abnormally developed in Scx knockout mice. These results establish the presence of an indispensable limb Scx+Hoxd13+ MSSC population and their differentiation into soft tissue progenitors (Scx+Col1a1+) and hard tissue progenitors (Scx+Sox9+). Collectively, this study paves the way for systematically decoding the complex molecular mechanisms and cellular programs of musculoskeletal tissues morphogenesis in limb development and regeneration.
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