Single nuclei transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration.

IF 3.7 2区社会学 Q2 ENVIRONMENTAL STUDIES Marine Policy Pub Date : 2024-07-26 DOI:10.1101/2023.06.23.546220

Simon Perrin, Maria Ethel, Vincent Bretegnier, Cassandre Goachet, Cécile-Aurore Wotawa, Marine Luka, Fanny Coulpier, Cécile Masson, Mickael Ménager, Céline Colnot

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Abstract

Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nuclei atlas of the periosteum at steady-state and of the fracture site during early stages of bone repair ( https://fracture-repair-atlas.cells.ucsc.edu ). We identified periosteal SSPCs expressing stemness markers ( Pi16 and Ly6a /SCA1) and responding to fracture by adopting an injury-induced fibrogenic cell (IIFC) fate, prior to undergoing osteogenesis or chondrogenesis. We identified distinct gene cores associated with IIFCs and their engagement into osteogenesis and chondrogenesis involving Notch, Wnt and the circadian clock signaling respectively. Finally, we show that IIFCs are the main source of paracrine signals in the fracture environment, suggesting a crucial paracrine role of this transient IIFC population during fracture healing. Overall, our study provides a complete temporal topography of the early stages of fracture healing and the dynamic response of periosteal SSPCs to injury, redefining our knowledge of bone regeneration.

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单核转录组学揭示了骨膜骨骼/干祖细胞在骨再生过程中的分化轨迹。

骨骼再生是由骨骼干细胞/祖细胞（SSPCs）介导的，骨骼干细胞/祖细胞主要是在骨骼损伤后从骨膜中招募的。人们对骨膜的组成以及 SSPC 的活化和分化步骤仍然知之甚少。在这里，我们生成了骨膜稳态和骨修复早期骨折部位的单核图谱( https://fracture-repair-atlas.cells.ucsc.edu )。我们鉴定了表达干性标记（Pi16和Ly6a /SCA1）的骨膜SSPCs，它们在进行骨生成或软骨生成之前，通过采用损伤诱导纤维细胞（IIFC）命运对骨折做出反应。我们确定了与 IIFCs 相关的不同基因核心，以及它们参与成骨和软骨形成的情况，这些基因核心分别涉及 Notch、Wnt 和昼夜节律钟信号转导。最后，我们发现 IIFCs 是骨折环境中旁分泌信号的主要来源，这表明瞬时 IIFCs 群体在骨折愈合过程中发挥着重要的旁分泌作用。总之，我们的研究为骨折愈合的早期阶段以及骨膜 SSPCs 对损伤的动态反应提供了完整的时间拓扑图，重新定义了我们对骨再生的认识。

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来源期刊

Marine Policy Multiple-

CiteScore

7.60

自引率

13.20%

发文量

428

期刊介绍： Marine Policy is the leading journal of ocean policy studies. It offers researchers, analysts and policy makers a unique combination of analyses in the principal social science disciplines relevant to the formulation of marine policy. Major articles are contributed by specialists in marine affairs, including marine economists and marine resource managers, political scientists, marine scientists, international lawyers, geographers and anthropologists. Drawing on their expertise and research, the journal covers: international, regional and national marine policies; institutional arrangements for the management and regulation of marine activities, including fisheries and shipping; conflict resolution; marine pollution and environment; conservation and use of marine resources. Regular features of Marine Policy include research reports, conference reports and reports on current developments to keep readers up-to-date with the latest developments and research in ocean affairs.