Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability

Yoshihiro Fukawatase; Masashi Toyoda; Kohji Okamura; Ken-ichi Nakamura; Kazuhiko Nakabayashi; Shuji Takada; Mayu Yamazaki-Inoue; Akira Masuda; Michiyo Nasu; Kenichiro Hata; Kazunori Hanaoka; Akon Higuchi; Kaiyo Takubo; Akihiro Umezawa

doi:10.1038/srep05421

Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability

Sci Rep. 2014 Jun 27:4:5421. doi: 10.1038/srep05421.

Authors

Affiliations

¹ 1] Department of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan [2] School of BioMedical Science, Tokyo Medical and Dental University, Tokyo, 113-0034, Japan.
² 1] Department of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan [2] Department of Research Team for Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
³ Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan.
⁴ Department of Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
⁵ Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan.
⁶ Department of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan.
⁷ Department of BioSciences, Kitasato University School of Science, Kanagawa, 252-0373, Japan.
⁸ 1] Department of Chemical and Materials Engineering, National Central University, Taoyuan, 32001, Taiwan [2] College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.

Abstract

Ataxia telangiectasia is a neurodegenerative inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. iPS cells lacking ATM (AT-iPS cells) exhibited hypersensitivity to X-ray irradiation, one of the characteristics of the disease. While parental ataxia telangiectasia cells exhibited significant chromosomal abnormalities, AT-iPS cells did not show any chromosomal instability in vitro for at least 80 passages (560 days). Whole exome analysis also showed a comparable nucleotide substitution rate in AT-iPS cells. Taken together, these data show that ATM is involved in protection from irradiation-induced cell death.

Publication types

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

MeSH terms

Animals
Apoptosis / radiation effects
Ataxia Telangiectasia / genetics
Ataxia Telangiectasia / pathology*
Ataxia Telangiectasia / radiotherapy
Ataxia Telangiectasia Mutated Proteins / genetics
Blotting, Western
Cell Differentiation / radiation effects
Cell Proliferation / radiation effects
Cells, Cultured
Cellular Reprogramming
Child
Chromosomal Instability / radiation effects*
Exome / genetics*
Fluorescent Antibody Technique
High-Throughput Nucleotide Sequencing
Humans
Immunoenzyme Techniques
In Situ Hybridization, Fluorescence
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Induced Pluripotent Stem Cells / radiation effects
Karyotyping
Male
Mice
Mice, Inbred NOD
Mice, SCID
RNA, Messenger / genetics
Radiation Tolerance / genetics*
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Teratoma / genetics
Teratoma / pathology*
Teratoma / radiotherapy
X-Rays

Substances

RNA, Messenger
ATM protein, human
Ataxia Telangiectasia Mutated Proteins

Associated data

GEO/GSE47498
GEO/GSM1151202
GEO/GSM1151203
GEO/GSM1151204
GEO/GSM1151205
GEO/GSM1151206
SRA/DRP001084