ESPE Abstracts

Recent studies demonstrate the pivotal roles that bone-making somatic stem cells – skeletal stem cells – play in skeletal development and growth. Subtle alterations in the skeletal stem cell compartment introduced genetically or epigenetically could amplify within their derivatives, resulting in aberrations of skeletal structures and functions. The emerging concept is that skeletal stem cells are not a monolithic group of cells with homogeneous identities. Instead, these stem cells represent a highly heterogeneous group of cells with region-specific functions. All the skeletal compartments known to play roles in growth and development, including the growth plate, perichondrium, periosteum, endosteum, bone marrow stroma, and suture, maintain their own stem cell populations. Recent cutting-edge assays, including ex vivo stem cell assays with refined cell surface markers, single-cell omics approaches, and most importantly, in vivo lineage-tracing studies with highly cell-type specific tracers, have all contributed to this updated concept. The prime example is the resting zone of the growth plate, which houses a population of PTHrP-expressing stem cells. These PTHrP+ stem cells can provide proliferating chondrocytes through asymmetric divisions, which can undergo hypertrophy and transformation into osteoblasts and stromal cells. Another example is Fgfr3+ stem cells in the endosteal space, which rapidly provide osteoblasts in young bones. Significantly, these stem cells can acquire tumorigenic properties upon mutations of crucial driver genes. This regional diversity of skeletal stem cells is developmentally inscribed within their cells-of-origins of the bone anlage. Recent studies highlight the emerging complexity of the skeletal cell lineage, presenting an updated model of stem cells of the matrix-embedded cell type.