Gene expression profiling of developing ovine embryonic fat tail tissues across nine stages (from E50 to E80) at single cell level
In mammals, whit adipose tissue (WAT) acts as the primary energy reservoir to modulate glucose and lipid homeostasis, and can also intervene several aspects of organismal physiology by endocrine manor. Hypertrophic development of WAT is associated with various metabolic disease, but hyperplastic adipogenesis is more responsible for metabolic health and distinct metabolic response across depots. However, our understating for cellular origins of adipocytes, the hierarchy of adipogenic progenitor population and the crucial regulons governing adipogenesis remains uncompleted. In this study, by constructing global gene expression and chromatin accessibility profiling for developing ovine fat tail tissue covering the whole stage of adipogenesis at single cell resolution, we identified several causal genes promoting adipogenesis and three cellular origins promising the congenital, repaid and massive fat deposition, including one progenitor and stem cell population (MCM5+/SFRP4+), two connective tissue progenitor clusters (COL6A6+/ALDH1A1+), and one vascular smooth muscle cell population (GUCY1B1+/RAI14+). Meanwhile, we also systemically investigated causal genes driving the dynamic specialization of angiogenesis, osteogenesis, chondrogenesis and myogenesis that accompanying fat tail development. Furthermore, by comprehensive integration of scRNA-seq and scATAC-seq data, we deciphered the enhancer-driver gene regulation networks (eGRNs) underpinning each lineage specialization in an unbiased manner. Collectively, our study broadens the understating for progenitor population hierarchy, enriches the available specific markers for various cell types, and provides new insights into cellular origins of adipocytes and molecular mechanism underpinning dynamic differentiation processes of multi lineages. Overall design: The embryonic ovine tail tissues at E50, E55, E60, E63, E66, E69, E72, E75 and E80 were used to make single cell suspension and perform scRNA-seq, one replicate each time point. Sheep breed, Tan sheep, a kind of fat tailed sheep.