Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations.

Content Provider	Europe PMC
Author	So, Seongjun Lee, Song Lee, Yeonmi Han, Jongsuk Kang, Soonsuk Choi, Jiwan Kim, Bitnara Kim, Deokhoon Yoo, Hyun-Ju Shim, In-Kyong Oh, Ju-Yun Lee, Yu-Na Kim, Song-Cheol Kang, Eunju
Copyright Year	2022
Abstract	Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.
ISSN	19766696
Journal	BMB Reports
Volume Number	55
PubMed Central reference number	PMC9537029
Issue Number	9
PubMed reference number	35651332
e-ISSN	1976670X
DOI	10.5483/BMBRep.2022.55.9.023
Language	English
Publisher	Korean Society for Biochemistry and Molecular Biology
Publisher Date	2022-09-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2022 by the The Korean Society for Biochemistry and Molecular Biology
Subject Keyword	Diabetes Human induced pluripotent stem cells Mitochondria mtDNA mutation Pancreatic cell differentiation
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry