Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells

Taisuke Kinoshita, Go Nagamatsu, Takeo Kosaka, Keiyo Takubo, Akitsu Hotta, James Ellis, Toshio Suda

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellular response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.

Original languageEnglish
Pages (from-to)321-326
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume407
Issue number2
DOIs
Publication statusPublished - 2011 Apr 8

Fingerprint

Ataxia Telangiectasia
Genomic Instability
Fibroblasts
Genes
DNA
Chromosomes
Gene expression
Tumors
Cells
Abnormal Karyotype
Germ Layers
Double-Stranded DNA Breaks
Tumor Suppressor Genes
Transcriptome
Cell Division
DNA Damage
Genome

Keywords

  • ATM
  • DNA damage
  • Pluripotency
  • Reprogramming

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells. / Kinoshita, Taisuke; Nagamatsu, Go; Kosaka, Takeo; Takubo, Keiyo; Hotta, Akitsu; Ellis, James; Suda, Toshio.

In: Biochemical and Biophysical Research Communications, Vol. 407, No. 2, 08.04.2011, p. 321-326.

Research output: Contribution to journalArticle

Kinoshita, Taisuke ; Nagamatsu, Go ; Kosaka, Takeo ; Takubo, Keiyo ; Hotta, Akitsu ; Ellis, James ; Suda, Toshio. / Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 407, No. 2. pp. 321-326.
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