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

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 (mt...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537029/
https://www.ncbi.nlm.nih.gov/pubmed/35651332
http://dx.doi.org/10.5483/BMBRep.2022.55.9.023
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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
author_facet 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
author_sort So, Seongjun
collection PubMed
description 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.
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spelling pubmed-95370292022-10-13 Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations 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 BMB Rep Article 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. Korean Society for Biochemistry and Molecular Biology 2022-09-30 2022-09-30 /pmc/articles/PMC9537029/ /pubmed/35651332 http://dx.doi.org/10.5483/BMBRep.2022.55.9.023 Text en Copyright © 2022 by the The Korean Society for Biochemistry and Molecular Biology https://creativecommons.org/licenses/by-nc/4.0/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 (https://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.
spellingShingle Article
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
Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations
title Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations
title_full Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations
title_fullStr Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations
title_full_unstemmed Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations
title_short Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations
title_sort dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial dna mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537029/
https://www.ncbi.nlm.nih.gov/pubmed/35651332
http://dx.doi.org/10.5483/BMBRep.2022.55.9.023
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