epiphyseal stem cell niche

SNIC 2022/23-228


SNIC Small Storage

Principal Investigator:

Andrei Chagin


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30108: Cell and Molecular Biology




Longitudinal bone growth in children is fueled by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification. However, how this continuous supply is maintained throughout the years of childhood growth remains unknown. Here, using clonal genetic tracing with multicolor reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondro-progenitors, whereas later in life, coinciding with the formation of the secondary ossification center, chondro-progenitors acquire the capacity for self-renewal, resulting in the formation of large and stable monoclonal columns of chondrocytes. Simultaneously, chondro-progenitors begin to express stem cell markers and undergo symmetric cell division. Expansion of the pool of self-renewing progenitors involves the mTORC1 signaling pathway. Our current findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, providing a continuous supply of chondrocytes over a prolonged period.