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Regional specialization and fate specification of bone stromal cells in skeletal development

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Sivaraj,  Kishor K.
Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Potente,  Michael
Angiogenesis & Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Citation

Sivaraj, K. K., Jeong, H.-W., Dharmalingam, B., Zeuschner, D., Adams, S., Potente, M., et al. (2021). Regional specialization and fate specification of bone stromal cells in skeletal development. CELL REPORTS, 36(2): 109352. doi:10.1016/j.celrep.2021.109352.


Cite as: https://hdl.handle.net/21.11116/0000-0008-F5EB-B
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 beta (PDGFR beta) signaling and the transcription factor Jun-B. The sum of our findings improves our understanding of BMSC development, lineage relationships, and differentiation.