DataVXAdvanced SciencePaper
journal article·2020-12Open access

Atlas of Musculoskeletal Stem Cells with the Soft and Hard Tissue Differentiation Architecture

Zi Yin, Junxin Lin, Ruojin Yan, Richun Liu, Mengfei Liu, Bo Zhou, Wenyan Zhou, Chengrui An, Yangwu Chen, Yejun Hu, Chunmei Fan, Kun Zhao, Bingbing Wu, Xiaohui Zou, Jin Zhang, Ahmed H. El‐Hashash, Xiao Chen, Hongwei Ouyang

Advanced Science· Volume 7· Issue 23
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Source abstract

Abstract

Abstract 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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Research context

OpenAlex topics: CAR-T cell therapy research · Biomedical and Engineering Education · Muscle Physiology and Disorders

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310058 China

Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China

China Orthopedic Regenerative Medicine (CORMed) Hangzhou 310058 China

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China

Zhejiang University‐University of Edinburgh Institute & School of Basic Medicine Zhejiang University School of Medicine Hangzhou 310058 China

Department of Gynecology the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310058 China

The First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine Department of Basic Medical Sciences School of Medicine Zhejiang University Hangzhou 310058 China

Edinburgh Medical School University of Edinburgh Edinburgh EH16 4SB UK

Department of Sports Medicine School of Medicine Zhejiang University Hangzhou 310058 China

Funding

National Natural Science Foundation of China

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