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.

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