TY - JOUR TI - Heterogeneity of murine periosteum progenitors involved in fracture healing AU - Matthews, Brya G AU - Novak, Sanja AU - Sbrana, Francesca V AU - Funnell, Jessica L AU - Cao, Ye AU - Buckels, Emma J AU - Grcevic, Danka AU - Kalajzic, Ivo A2 - Mohan, Subburaman A2 - Rosen, Clifford J VL - 10 PY - 2021 DA - 2021/02/09 SP - e58534 C1 - eLife 2021;10:e58534 DO - 10.7554/eLife.58534 UR - https://doi.org/10.7554/eLife.58534 AB - The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched with progenitor cells, including Sca1+ cells, fibroblast colony-forming units, and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that alpha smooth muscle actin (αSMA) identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture can be targeted by αSMACreER. Previously identified skeletal stem cell populations were common in periosteum but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched with skeletal progenitor cells, and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing. KW - fracture KW - periosteum KW - skeletal stem cell KW - pdgfra KW - alpha smooth muscle actin KW - osteoblast JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -