Regional specialization and fate specification of bone stromal cells in skeletal development
0301 basic medicine
osteoblast lineage cells
Transcription, Genetic
QH301-705.5
adipocytes
Article
Bone and Bones
Receptor, Platelet-Derived Growth Factor beta
Mice
03 medical and health sciences
diaphysis
Animals
Cell Lineage
Biology (General)
metaphysis
0303 health sciences
Bone Development
Endothelial Cells
Cell Differentiation
Mesenchymal Stem Cells
bone mesenchymal stromal cells
mouse genetics
Mice, Inbred C57BL
Animals, Newborn
Cardiovascular and Metabolic Diseases
Organ Specificity
Single-Cell Analysis
Stromal Cells
Signal Transduction
DOI:
10.1016/j.celrep.2021.109352
Publication Date:
2021-07-13T15:05:51Z
AUTHORS (7)
ABSTRACT
Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also to fracture healing and disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture of different subpopulations with distinct molecular and functional properties. The lineage relationship between BMSC subsets and their regulation by intrinsic and extrinsic factors are not well understood. Here, we show with mouse genetics, ex vivo cell differentiation assays, and transcriptional profiling that BMSCs from metaphysis (mpMSCs) and diaphysis (dpMSCs) are fundamentally distinct. Fate-tracking experiments and single-cell RNA sequencing indicate that bone-forming osteoblast lineage cells and dpMSCs, including leptin receptor-positive (LepR+) reticular cells in bone marrow, emerge from mpMSCs in the postnatal metaphysis. Finally, we show that BMSC fate is controlled by platelet-derived growth factor receptor β (PDGFRβ) signaling and the transcription factor Jun-B. The sum of our findings improves our understanding of BMSC development, lineage relationships, and differentiation.
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CITATIONS (78)
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