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

• DOI: 10.1016/j.celrep.2021.109352
• Publication Date: 2021-07-13T15:05:51Z
• Authors: Kishor K. Sivaraj; Hyun-Woo Jeong; Backialakshmi Dha...; Dagmar Zeuschner; Susanne Adams; Michael Potente; Ralf H. Adams
• Keywords: Cell fate determination

Bone stroma contributes to the regulation of osteogenesis and hematopoiesis but also fracture healing disease processes. Mesenchymal stromal cells from bone (BMSCs) represent a heterogenous mixture different subpopulations with distinct molecular functional properties. The lineage relationship between BMSC subsets their by intrinsic extrinsic factors are not well understood. Here, we show mouse genetics, ex vivo cell differentiation assays, transcriptional profiling that BMSCs metaphysis (mpMSCs) diaphysis (dpMSCs) fundamentally distinct. Fate-tracking experiments single-cell RNA sequencing indicate bone-forming osteoblast dpMSCs, including leptin receptor-positive (LepR+) reticular in marrow, emerge mpMSCs postnatal metaphysis. Finally, fate is controlled platelet-derived growth factor receptor β (PDGFRβ) signaling transcription Jun-B. sum our findings improves understanding development, relationships, differentiation.