ArticleThe Journal of clinical investigation2024
Itm2a expression marks periosteal skeletal stem cells that contribute to bone fracture healing.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed.
- Skeletal stem and progenitor cell niche organization, regulation and repair.Reviews in endocrine & metabolic disorders · 2026Review
- The emerging roles of ITM2A: At the molecular crossroads of development and pathogenesis.iScience · 2026Review
- The role and therapeutic potential of vitamins in fracture healing.Nutrition journal · 2026Review
- Fgf18 marks reserve skeletal progenitors in the fibrous periosteum contributing to bone fracture repair.Cell reports · 2026Article
- ITM2A promotes thyroid cancer differentiation through metabolic reprogramming and enhances PD-L1-dependent T-cell responses.Clinical and experimental medicine · 2026Article
- Chondrocytes in fracture healing: A review of chondrocyte journey.Chinese medical journal · 2026Review
- IL-1β/EPAS1-Associated Ferroptotic Stress Impairs Skeletal Stem/Progenitor Cell Function in Inflammation-Associated Fracture Nonunion.Current issues in molecular biology · 2026Article
- Macrophage piezo1 senses mechanical force to drive osteoclastogenesis via ZBP1: Implications for bone remodelling therapy.Clinical and translational medicine · 2026Article
- Periosteal mitochondria DNA structures drive aging-associated poor skeletal repair.Bone research · 2026Article
- Fibrous-layer resident Angptl7Cell research · 2026Article
- Fibrous-layer periosteal stem cells sensing injury-induced inflammation.Cell research · 2026Article
- Mapping the Tissue-of-Origins of Mesenchymal Stromal Cells in Injury Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Current state of bioceramic bone repair materials in immune regulation: a review.Frontiers of medicine · 2025Review
- Article
- Single-cell mapping reveals age-related alterations in periosteal progenitor cells and immune microenvironment.Cell regeneration (London, England) · 2025Article
- Article
- Single-cell profiling reveals periosteal signatures of impaired periosteal cells proliferation in a drill-hole model of type 2 diabetes.Cell communication and signaling : CCS · 2025Article
- EGR1 Promotes Craniofacial Bone Regeneration via Activation of ALPL⁺PDGFD⁺ Periosteal Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Harnessing the diversity and potential of endogenous skeletal stem cells for musculoskeletal tissue regeneration.Stem cells (Dayton, Ohio) · 2025Review
- T cell related osteoimmunology in fracture healing: Potential targets for augmenting bone regeneration.Journal of orthopaedic translation · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
The periosteum contains skeletal stem/progenitor cells that contribute to bone fracture healing. However, the in vivo identity of periosteal skeletal stem cells (P-SSCs) remains unclear, and membrane protein markers of P-SSCs that facilitate tissue engineering are needed. Here, we identified integral membrane protein 2A (Itm2a) enriched in SSCs using single-cell transcriptomics. Itm2a+ P-SSCs displayed clonal multipotency and self-renewal and sat at the apex of their differentiation hierarchy. Lineage-tracing experiments showed that Itm2a selectively labeled the periosteum and that Itm2a+ cells were preferentially located in the outer fibrous layer of the periosteum. The Itm2a+ cells rarely expressed CD34 or Osx, but expressed periosteal markers such as Ctsk, CD51, PDGFRA, Sca1, and Gli1. Itm2a+ P-SSCs contributed to osteoblasts, chondrocytes, and marrow stromal cells upon injury. Genetic lineage tracing using dual recombinases showed that Itm2a and Prrx1 lineage cells generated spatially separated subsets of chondrocytes and osteoblasts during fracture healing. Bone morphogenetic protein 2 (Bmp2) deficiency or ablation of Itm2a+ P-SSCs resulted in defects in fracture healing. ITM2A+ P-SSCs were also present in the human periosteum. Thus, our study identified a membrane protein marker that labels P-SSCs, providing an attractive target for drug and cellular therapy for skeletal disorders.
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