The bone derived from scl-progenitors micromass forms bone marrow [scRNAseq]

Current strategy to derive mouse sclerotomal progenitors suffered from low differentiation efficiency and heterogenous cell progenies. Here, we developed a fast and efficient strategy to generate sclerotomal progenitors from murine embryonic stem cells (mESCs).

Naïve mESCs were differentiated through epiblast-like cells (EpiLCs) and primitive streak, and the sclerotomal fate was directly induced from primitive streak by modulating BMP and SHH signaling, achiving an 85.8% differentiation efficiency. Moreover, the resulting progenitors showed similar global gene expression profiles as primary sclerotome, possessed strong osteochondral bipotential and could recapitulate key features of endochondral ossification upon micromass-mediated osteogenic induction, including bone marrow niche regeneration.