Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene

Xianming Wang; Shen Chen; Ingo Burtscher; Michael Sterr; Anja Hieronimus; Fausto Machicao; Harald Staiger; Hans-Ulrich Häring; Gabriele Lederer; Thomas Meitinger; Heiko Lickert

doi:10.1016/j.scr.2016.08.005

Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene

Stem Cell Res. 2016 Sep;17(2):292-295. doi: 10.1016/j.scr.2016.08.005. Epub 2016 Aug 6.

Authors

Affiliations

¹ Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Stem Cell Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Technische Universität München, Ismaninger straße 22, 81675 München, Germany.
² iPS and Cancer Research Unit, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
³ Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Stem Cell Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
⁴ Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen, 72076 Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tübingen, 72076 Tübingen, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
⁵ Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
⁶ Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen, 72076 Tübingen, Germany; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, 72076 Tübingen, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
⁷ Institute of Human Genetics, Technische Universität München, 81675 München, Germany.
⁸ Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, 81675 München, Germany.
⁹ Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Stem Cell Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Technische Universität München, Ismaninger straße 22, 81675 München, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany. Electronic address: [email protected].

PMID: 27879214
DOI: 10.1016/j.scr.2016.08.005

Abstract

Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor PDX1 leads to pancreatic agenesis, whereas certain heterozygous point mutations are associated with Maturity-Onset Diabetes of the Young 4 (MODY4) and Type 2 Diabetes Mellitus (T2DM). To understand the pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a C18R heterozygous mutation in the transactivation domain of PDX1. The resulting PDX1 C18R iPSCs generated by episomal reprogramming are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Taken together, this iPSC line will be useful to study diabetes pathomechanisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Cell Differentiation
Cells, Cultured
Cellular Reprogramming*
DNA Mutational Analysis
Diabetes Mellitus, Type 2 / genetics
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / pathology*
Female
Fibroblasts / cytology
Fibroblasts / metabolism
Genotype
Heterozygote
Homeodomain Proteins / genetics*
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Induced Pluripotent Stem Cells / transplantation
Karyotype
Microscopy, Fluorescence
Polymorphism, Single Nucleotide
Trans-Activators / genetics*
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Homeodomain Proteins
Trans-Activators
Transcription Factors
pancreatic and duodenal homeobox 1 protein

Supplementary concepts

Mason-Type Diabetes