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

• Published in: Scientific reports Vol. 12; no. 1; p. 4740
• Main Authors: Hiyoshi, Hideyuki, Sakuma, Kensuke, Tsubooka-Yamazoe, Noriko, Asano, Shinya, Mochida, Taisuke, Yamaura, Junji, Konagaya, Shuhei, Fujii, Ryo, Matsumoto, Hirokazu, Ito, Ryo, Toyoda, Taro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/61/2035; 631/61/2320; 631/61/490; 692/699/317; Cell Differentiation; Cell therapy; Diabetes; Diabetes mellitus; Endocrine Cells; Fibroblast growth factor receptor 2; Humanities and Social Sciences; Humans; Induced Pluripotent Stem Cells; Islet cells; Islets of Langerhans - metabolism; Mucoproteins - metabolism; multidisciplinary; Oncogene Proteins - metabolism; Pancreas; Pluripotency; Pluripotent Stem Cells; Polo-like kinase 1; Science; Science (multidisciplinary); Stem cells; Transcriptomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-08753-5

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.