External lunch seminar: Andrei Chagin
“A radical switch in clonality reveals the formation of a stem cell niche in the epiphyseal growth plate”
The majority of disorders that influence final height involve thin cartilage discs, called growth or epiphyseal plates, which are located near the ends of all growing long bones. Growth plates provide a continuous supply of the cells crucial for the maintenance of normal bone growth but it is not yet known how these discs maintain themselves. The generally accepted view is that chondro-progenitors within the structure are responsible for this maintenance and that consumption of these progenitors leads to the fusion of the growth plate and the cessation of growth. However, this has never been functionally proven.
Employing clonal genetic tracing, we show here that in mice longitudinal growth during the fetal and neonatal periods occurs via small clones arranged into multi-clonal columns, a pattern of clonality that strongly supports direct depletion of the progenitor cells. In contrast, later in life this pattern changes dramatically, with the formation of mono-clonal chondrocyte columns and a 2-5 fold increase in clone size. Since no other drastic changes in cell kinetics could be observed this radical switch in clonality suggests that chondro-progenitors acquire the capacity for self-renewal. Interestingly, this acquisition occurs simultaneously with the formation of the secondary ossification center, the expression of stem cell markers and initiation of symmetric cell divisions. Furthermore, the pool of self-renewing progenitors could be expanded by specifically activating the mTORC1-signaling pathway in the growth plate, suggesting a novel target for the treatment of growth disorders.
Overall our present findings suggest that a stem cell niche develops postnatally in the epiphyseal growth plate and that this niche is essential for the maintenance of postnatal bone growth.Contact person: Elisa Floriddia