CD82 is a marker to isolate β cell precursors from human iPS cells and plays a role for the maturation of β cells

Generation of pancreatic beta cells from pluripotent stem cells is a key technology to develop cell therapy for insulin-dependent diabetes and considerable efforts have been made to produce beta cells. However, due to multiple and lengthy differentiation steps, production of beta cells is often unstable. It is also desirable to eliminate undifferentiated cells to avoid potential risks of tumorigenesis. To isolate beta cell precursors from late stage pancreatic endocrine progenitor (EP) cells derived from iPS cells, we have identified CD82, a member of the tetraspanin family. CD82(+) cells at the EP stage differentiated into endocrine cells more efficiently than CD82(-) EP stage cells. We also show that CD82(+) cells in human islets secreted insulin more efficiently than CD82(-) cells. Furthermore, knockdown of CD82 expression by siRNA or inhibition of CD82 by monoclonal antibodies in NGN3(+) cells suppressed the function of beta cells with glucose-stimulated insulin secretion, suggesting that CD82 plays a role in maturation of EP cells to beta cells.

Automated summary

Generating pancreatic beta cells from pluripotent stem cells is crucial for developing cell therapy for insulin-dependent diabetes, but the process often faces challenges such as instability and potential risk of tumorigenesis. By isolating beta cell precursors from late stage pancreatic endocrine progenitor cells, the tetraspanin family member CD82 has been identified as playing a key role in the efficient differentiation and function of beta cells. Knockdown or inhibition of CD82 expression also affects the maturation of EP cells into beta cells.