Interfering with DNA replication improves beta cell differentiation and maturation from human pluripotent stem cells
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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Cell cycle progression plays an important role in mediating the transition from a differentiated state to a pluripotent stem cell. Conversely, establishing limitations in proliferative potential may be important to achieve functional maturity as well as to prevent abnormal growths after transplantation of stem cell derived products. Here we induced exit from the cell cycle in pancreatic progenitors by interfering with the progression of DNA replication and determined growth potential, differentiation and maturation to insulin producing endocrine cells. Treatment with the DNA polymerase inhibitor aphidicolin, as well as with antineoplastic agents, etoposide and cisplatin arrested cell cycle progression in G1 and promoted differentiation of pancreatic progenitor cells towards C-peptide positive cells. G1 arrest by aphidicolin did not induce DNA damage response or apoptosis, improved the functional maturity of stem cell-derived cells and protected mice from diabetes, without the formation of cystic growths. Therefore, induction of G1 arrest is an efficient way to promote precursor cell differentiation and generate insulin-producing cells with a stable identity and predictable growth potential after transplantation.
提供机构：
Regeneron Pharmaceuticals, Tarrytown, New York, USA
创建时间：
2022-02-20
