Single cell transcriptomic understanding of the human endochondral ossification process

During development and repair, bones pre-dominantly form through the endochondral ossification route. This involves the condensation of mesenchymal cells, forming a cartilage tissue progressively vascularized and remodeled into a mature Bone Organ, hosting functional hematopoiesis.
This endochondral process has been successfully recapitulated using human Mesenchymal Stromal/Stem Cells (hMSCs). By priming hMSCs in vitro to form cartilage, the tissue naturally remodels into bone and bone marrow following in vivo implantation in mice. This provides an ideal model to study the cellular & molecular mechanisms involved in Bone formation. In particular, human mesenchymal cells remain poorly characterized as a population, and their cellular heterogeneity and associated differentiation potential remain to be deciphered. In this project, we aim at understanding the cellular diversity of human mesenchymal cells during the time course of endochondral bone formation. This will allow to understand what populations can drive the formation of cartilage, bone and later on support the maintenance of hematopoietic cells. Subpopulations will be identified and their progressive lineage restrictions or stem cell maintenance along the endochondral ossification will be elucidated.