Unveiling cellular heterogeneity in early beige adipogenesis by single cell RNA-seq
Beige adipocytes are thermogenic adipocytes that appear in white adipose tissues and have a potential to counteract obesity and metabolic diseases. Although multiple molecular players in beige adipogenesis have been reported, understanding of dynamic transcriptional programs along differentiation is limited due to cellular heterogeneity. Here, we present single cell RNA sequencing (scRNA-seq) analysis of PDGFRA+ adipocyte precursor cells obtained from inguinal adipose tissues treated with a beta3 adrenergic receptor agonist, an inducer of beige adipogenesis. This scRNA-seq analysis enabled identification of four subpopulations of the precursor cells. Using the interrelationships among the subpopulations, we identified the differentiation trajectory during early beige adipogenesis. The differentiation trajectory revealed serial activation of intracellular signaling pathways required for early beige adipogenesis. Therefore, our scRNA-seq analysis provides new insights into the differentiation trajectory of PDGFRA+ adipocyte precursors, as well as signaling cascades that represent and regulate the cellular transition along the differentiation trajectory.