Prof.Hongwei Ouyang's group published on Advanced Science
来源 ：基础医学系 发布时间 ：2020-11-17 浏览次数 ：278
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, andCol1a1). This is confirmed by genetic in vivo lineage tracing. Moreover, single‐cell analyses of Scx knockout mice tissues illustrates thatScxregulates MSSC self‐ enewal and proliferation potential. A high‐ hroughput and low‐cost multi‐ issues 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.
