SCJS

[SCJS-02] Recapitulation of skeletal development using human pluripotent stem cells and its application

〇Shinsuke Ohba¹ (1. Dept Tissue Dev Biol, Osaka Univ Grad Sch Dent)

Keywords:多能性幹細胞、骨、軟骨

Epigenetic landscape model, proposed by Conrad H. Waddington, indicates that gene expression and epigenome underlie cell fate specification in development. We have been trying to clarify gene regulatory networks (GRNs) that specify skeletal cells and to understand molecular mechanisms underlying the skeletal program. We have not only performed genome-wide analyses on mouse skeletal cells, but also develop skeletal development-modeling systems using human pluripotent stem cells (hPSCs). We recently developed hPSC-based methods that recapitulate the physiological endochondral ossification process (Tani S et al. Cell Rep, 2023); endochondral bone-like structures were induced by implanting hPSC-derived sclerotome into mouse renal capsules. Single-cell RNA-sequence revealed that the structures were composed of human skeletal cells and mouse endothelial and blood cells. Trajectory analysis suggested differentiation of osteo-chondroprogenitors into osteoblasts and chondrocytes in the structures. Single-cell multiome, which can analyze both chromatin accessibilities and gene expressions at a single-cell level, enabled us to predict GRNs in the structures; the GRNs potentially contribute to human skeletal development. Thus, our method will contribute to recapitulation and understanding of developmental processes and disorders in skeleton.