Novel stem cells drive skeletal growth

Children grow in height through the activity of the growth plates, tiny discs of cartilage located near the ends of long bones. Growth plates must continuously supply large number of chondrocytes. This process involves a newly-discovered epiphyseal stem cells (epSCs) and their niche.

This discovery, which has changed our concept of longitudinal growth, will be explored further here.We will elucidate whether the renewal of epSCs is invariant or involves population asymmetry.

This will be address by combining clonal lineage tracing in Col2-CreERT:R26-Confetti mice, mathematical analysis of clonal dynamics and intravital two-photon microscopy.

The composition of the stem cell niche in both mice and humans will be explored utilizing single-cell 10X and slide-seq spatial transcriptomics, thus providing the unbiased spatial transcriptional landscape around the stem cells and identifying potential interactions. For human experiments, biopsies from children undergoing epiphysiodesis surgery will be utilized.

Finally, we will investigate the regulation of epSCs by growth hormone, which is widely used to treat growth retardation, but not always effective.

This regulation will be examined both in PTHrP-CreERT:tdTomato mice and cultured explants of human growth plates.Our findings will provide detailed insights into the cellular and molecular mechanisms regulating novel stem cells and establishing their fundamental role in skeletal growth.