Cell Fate Determining Molecular Switches and Signaling Pathway in Pax7-expressing Somitic Mesoderm

During development, different cell types are originated from a common progenitor at a specific time frame. Previous lineage tracing of Pax7+ progenitors in somitic mesoderm has built the foundation of its development trajectory towards dermis, brown adipocytes, and skeletal muscle at dorsal trunk. Yet the molecular switches and mechanisms of such differentiation remain unknown. By combining inducible lineage tracing and single-cell RNA sequencing, here we show the transcriptomic profile of the Pax7 lineage, precise differentiation time point, and transcription factors that could drive lineage-specific differentiation. Utilizing surface markers identified in each cell types, we successfully enriched brown adipocytes, dermal fibroblasts, and cell-type specific progenitors for in vitro culture. Further characterization has shown the importance of Wnt5a and Rgcc for lineage development during embryogenesis. We also propose eFAP (embryonic fibro/adipogenic progenitor) that resembles adult FAPs lineage potentials. The work provides further understanding of the Pax7 lineage during embryonic development. Overall design: Investigate the developmental trajectory of the Pax7 lineage during mouse embryogenesis at single-cell level. Bulk samples for specific population were investigated as well.