PhD Student The Chinese University of Hong Kong (CUHK) Hong kong, Hong Kong
Abstract: Brown adipocytes (BAs) and skeletal muscle in the trunk arise from a common PAX3+ progenitor cell derived from the paraxial mesoderm. PAX3+ cells transition through a MYF5+ state before developing into thermogenic brown adipocytes (BAs) but alternate pathways of BA development have not been described. Using single-cell transcriptomic profiles of human pluripotent stem cell (hPSC)-derived trunk organoids we identify a second, MYF5-independent, pathway for BA development that originates from the same PAX3+ progenitor previously shown to be important for BA development. The alternate BA pathway involves the transition from a PAX3+ state to one marked by EBF2, TGFBI and MEF2C. Guided by this analysis, two distinct pathways for BA development were reproduced by 2-dimensional, lineage-specific differentiation of hPSC-derived PAX3+ progenitors. Time-course, single cell RNA sequencing and velocity analysis revealed that although both EBF2+ and MYF5+ BA progenitors differentiate efficiently into BAs, they exhibit different capacities for producing vascular endothelial and skeletal muscle derivatives, respectively. Furthermore, single-cell transcriptomic comparison with existing dataset from Carnegie Stage 10-16 human embryos confirms these findings. This work highlights the utility of using organoids to understand human BA development.
Funding Source: The Hong Kong Jockey Club Charities Trust
