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

IF 6.4 1区生物学 Q1 BIOLOGY

eLife Pub Date : 2024-12-06 DOI:10.7554/eLife.92519

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-nucleus atlas of the periosteum at steady state and of the fracture site during the 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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来源期刊

eLife BIOLOGY-

CiteScore

12.90

自引率

3.90%

发文量

3122

审稿时长

17 weeks

期刊介绍： eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.