STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism

The STARD10 gene encodes for a lipid transfer protein and is associated with type 2 diabetes (T2D) risk and β cell function. However, the role of STARD10 in human β cell development and function are still unclear. Here, we deleted STARD10 in human embryonic stem cells and differentiated them into β-like cells. The deletion of STARD10 reduced the formation of INS⁺ β-like cells and proliferation. Lipidomics analyses revealed that STARD10-null β-like cells had higher triglyceride levels. Consistently, the expression levels of ETFB, which is involved in fatty acid β-oxidation, were severely reduced in STARD10-null β-like cells. STARD10-null β-like cells also had reduced glycolytic function, mitochondrial oxidative phosphorylation, and palmitate oxidation, which can likely contribute to slower proliferation and β cell dysfunction. Overall, our findings provided further insights into the role of STARD10 in human β cell development and function, and how its loss-of-function can contribute to increased T2D risk.