Molecular characterization of heterogeneous adipogenic progenitors
Abstract
Obesity, a metabolic syndrome caused by abnormal and ectopic accumulation of adipose tissue (fat), has become a global health problem that affects billions of people. Understanding the developmental process of adipose tissue including the stem and progenitor cells that give rise to adipocytes is crucial for effective control of ectopic fat accumulation. This project aims to dissect the molecular signatures of progenitors that give rise to intramuscular fat (IMF), white adipose tissue (WAT) and brown adipose tissue (BAT). We found that adipogenic progenitors are more enriched in slow compared to fast muscles. Cre/LoxP-mediated genetic cell-lineage labeling demonstrated that BAT progenitors are derived from a Myf5+/ Pax3+ lineage, IMF are derived from Myf5 –/Pax3– lineage and WAT are from a Myf5+/Pax3 +– lineage dependence. Diphtheria toxin-mediated genetic cell-lineage ablation confirmed that Myf5 and Pax3 expressions occur in BAT progenitor cells or their ancestors prior to adipose differentiation. In addition, ablation of Myf5+ myogenic lineage enhanced IMF adipogenesis, suggesting that myogenesis inhibits adipogenesis. By contrast, ablation of αP2+ adipogenic lineage revealed that adipogenesis is required for healthy myogenesis. In old mice, impaired myogenesis is accompanied by accumulation of adipocytes. Finally, we confirm that Dlk1 inhibits adipogenic differentiation of both IMF and BAT. Our study reveals surprising heterogeneity of adipogenic progenitors and the molecular regulation of distinct categories of adipose tissues, and provides novel insights into stem cell based approaches to the prevention and alleviation of obesity.
Degree
M.S.
Advisors
Kuang, Purdue University.
Subject Area
Biology
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