Differentiation of white and brown adipocytes from human pluripotent stem cells

Given the rapid increase in the prevalence of obesity and related metabolic diseases, research to better understand adipose tissue biology and physiology has garnered considerable attention. Adipose has been studied using both cell culture systems and model organisms. However, the mechanisms of adipocyte regulation are not comprehensively understood, as currently available in vitro or in vivo systems do not fully recapitulate human metabolic processes. Human primary adipocytes are difficult to culture and expand, and current cell systems have limitations such as cell line-to-cell line variability for adipocyte differentiation, decreased proliferation, and differentiation potential upon continued passaging. To overcome these limitations, we developed and established an efficient and robust adipocyte differentiation protocol using human pluripotent stem cells (hPSCs) and inducible expression of key adipogenic transcriptional regulators. Here, we provide a simple and stepwise protocol for programming hPSCs into mature white or brown adipocytes.