AIMP3 depletion causes genome instability and loss of stemness in mouse embryonic stem cells

Sun Mi Kim, Yoon Jeon, Doyeun Kim, Hyonchol Jang, June Sung Bae, Mi Kyung Park, Hongtae Kim, Sunghoon Kim, Ho Lee

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aminoacyl-tRNA synthetase-interacting multifunctional protein-3 (AIMP3) is a component of the multi-aminoacyl-tRNA synthetase complex and is involved in diverse cellular processes. Given that AIMP3 deficiency causes early embryonic lethality in mice, AIMP3 is expected to play a critical role in early mouse development. To elucidate a functional role of AIMP3 in early mouse development, we induced AIMP3 depletion in mouse embryonic stem cells (mESCs) derived from blastocysts of AIMP3f/f; CreERT2 mice. In the present study, AIMP3 depletion resulted in loss of self-renewal and ability to differentiate to three germ layers in mESCs. AIMP3 depletion led to accumulation of DNA damage by blocking double-strand break repair, in particular homologous recombination. Through microarray analysis, the p53 signaling pathway was identified as being activated in AIMP3-depleted mESCs. Knockdown of p53 rescued loss of stem cell characteristics by AIMP3 depletion in mESCs. These results imply that AIMP3 depletion in mESCs leads to accumulation of DNA damage and p53 transactivation, resulting in loss of stemness. We propose that AIMP3 is involved in maintenance of genome stability and stemness in mESCs.

Original languageEnglish
Article number972
JournalCell Death and Disease
Volume9
Issue number10
DOIs
Publication statusPublished - 2018 Oct 1

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Kim, S. M., Jeon, Y., Kim, D., Jang, H., Bae, J. S., Park, M. K., Kim, H., Kim, S., & Lee, H. (2018). AIMP3 depletion causes genome instability and loss of stemness in mouse embryonic stem cells. Cell Death and Disease, 9(10), [972]. https://doi.org/10.1038/s41419-018-1037-4