具有软硬组织分化架构的肌肉骨骼干细胞图谱,Advanced Science

当前位置： X-MOL 学术 › Adv. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

具有软硬组织分化架构的肌肉骨骼干细胞图谱
Advanced Science ( IF 15.1 ) Pub Date : 2020-10-22 , DOI: 10.1002/advs.202000938
Zi Yin _{1,

2,

3} , Junxin Lin _{2,

4} , Ruojin Yan _{2,

4} , Richun Liu _{2,

4} , Mengfei Liu _{2,

4} , Bo Zhou _{2,

4} , Wenyan Zhou _{2,

4,

5} , Chengrui An _{2,

4} , Yangwu Chen _{2,

4} , Yejun Hu _{2,

4} , Chunmei Fan _{1,

2} , Kun Zhao _{2,

4} , Bingbing Wu _{2,

4} , Xiaohui Zou _{2,

6} , Jin Zhang ₇ , Ahmed H El-Hashash _{5,

8} , Xiao Chen _{2,

3,

4,

9} , Hongwei Ouyang _{2,

3,

4,

5,

9}

Affiliation

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.

尽管干细胞身份和肌肉骨骼祖细胞的分层组织对于人类健康和行动能力至关重要，但在很大程度上仍未得到探索。在这里，通过高通量单细胞 RNA 测序分析了来自 E10.5、E12.5 和 E15.5 小鼠肢体的细胞，以说明肢体发育过程中的细胞结构。单细胞转录分析通过肌肉骨骼标记物（scleraxis [ Scx ]、Hoxd13、Sox9和Col1a1）的表达模式展示了肌肉骨骼干细胞 (MSSC)、软组织和硬组织祖细胞的身份和分化结构。这已通过体内遗传谱系追踪得到证实。此外，Scx 敲除小鼠组织的单细胞分析表明Scx调节 MSSC 的自我更新和增殖潜力。高通量、低成本的多组织RNA测序策略进一步提供了证据，证明Scx基因敲除小鼠的肌肉骨骼系统组织，包括肌肉、骨骼、半月板和软骨，均发育异常。这些结果证实了不可或缺的肢体 Scx+Hoxd13+ MSSC 群体的存在及其分化为软组织祖细胞 ( Scx+Col1a1+ ) 和硬组织祖细胞 ( Scx+Sox9+ )。总的来说，这项研究为系统地解码肢体发育和再生中肌肉骨骼组织形态发生的复杂分子机制和细胞程序铺平了道路。

"点击查看英文标题和摘要"

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

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.

更新日期：2020-12-03

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>