Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.
Mesenchymal progenitors (MPs) are considered to play vital roles in bone development, growth, bone turnover, and repair. In recent years, benefiting from advanced approaches such as single-cell sequence, lineage tracing, flow cytometry, and transplantation, multiple MPs are identified and characterized in several locations of bone, including perichondrium, growth plate, periosteum, endosteum, trabecular bone, and stromal compartment. However, although great discoveries about skeletal stem cells (SSCs) and progenitors are present, it is still largely obscure how the varied landscape of MPs from different residing sites diversely contribute to the further differentiation of osteoblasts, osteocytes, chondrocytes, and other stromal cells in their respective destiny sites during development and regeneration. Here we discuss recent findings on MPs’ origin, differentiation, and maintenance during long bone development and homeostasis, providing clues and models of how the MPs contribute to bone development and repair.
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