Characterization and reduction of non-endocrine cells accompanying islet-like endocrine cells differentiated from human iPSC

ヒトiPS細胞から作製した膵島様細胞に混入する目的外細胞の特性評価にもとづく除去. 京都大学プレスリリース. 2022-04-07.Elimination of non-target cells mixed into islet-like cells generated from human iPS cells based on characterization. 京都大学プレスリリース. 2022-04-15.The differentiation of pancreatic endocrine cells from human pluripotent stem cells has been thoroughly investigated for their application in cell therapy against diabetes. Although non-endocrine cells are inevitable contaminating by-products of the differentiation process, a comprehensive profile of such cells is lacking. Therefore, we characterized non-endocrine cells in iPSC-derived pancreatic islet cells (iPIC) using single-cell transcriptomic analysis. We found that non-endocrine cells consist of (1) heterogeneous proliferating cells, and (2) cells with not only pancreatic traits but also liver or intestinal traits marked by FGB or AGR2. Non-endocrine cells specifically expressed FGFR2, PLK1, and LDHB. We demonstrated that inhibition of pathways involving these genes selectively reduced the number of non-endocrine cells in the differentiation process. These findings provide useful insights into cell purification approaches and contribute to the improvement of the mass production of endocrine cells for stem cell-derived cell therapy for diabetes