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Publication : Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis.

First Author  Matsushita Y Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  2383
PubMed ID  37185464 Mgi Jnum  J:335639
Mgi Id  MGI:7483768 Doi  10.1038/s41467-023-38034-2
Citation  Matsushita Y, et al. (2023) Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis. Nat Commun 14(1):2383
abstractText  The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR)(+) perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear. Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 (Fgfr3) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. These Fgfr3-creER-marked endosteal stromal cells contribute to a stem cell fraction in young stages, which is later replaced by Lepr-cre-marked stromal cells in adult stages. Further, Fgfr3(+) endosteal stromal cells give rise to aggressive osteosarcoma-like lesions upon loss of p53 tumor suppressor through unregulated self-renewal and aberrant osteogenic fates. Therefore, Fgfr3(+) endosteal SSCs are abundant in young bone marrow and provide a robust source of osteoblasts, contributing to both normal and aberrant osteogenesis.
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