Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells

Masayuki Yamashita, Eriko Nitta, Go Nagamatsu, Yoshiko Matsumoto Ikushima, Kentaro Hosokawa, Fumio Arai, Toshio Suda

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Nucleostemin is a nucleolar protein known to play a variety of roles in cell-cycle progression, apoptosis inhibition, and DNA damage protection in embryonic stem cells and tissue stem cells. However, the role of nucleostemin in hematopoietic stem cells (HSCs) is yet to be determined. Here, we identified an indispensable role of nucleostemin in mouse HSCs. Depletion of nucleostemin using short hairpin RNA strikingly impaired the self-renewal activity of HSCs both in vitro and in vivo. Consistently, nucleostemin depletion triggered apoptosis rather than cell-cycle arrest in HSCs. Furthermore, DNA damage accumulated during cultivation upon depletion of nucleostemin. The impaired self-renewal activity of HSCs induced by nucleostemin depletion was partially rescued by p53 deficiency but not by p16Ink4a or p19Arf deficiency. Taken together, our study demonstrates that nucleostemin protects HSCs from DNA damage accumulation and is required for the maintenance of HSCs.

Original languageEnglish
Pages (from-to)196-201
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume441
Issue number1
DOIs
Publication statusPublished - 2013 Nov 8

Fingerprint

Hematopoietic Stem Cells
Stem cells
Maintenance
DNA Damage
Apoptosis
DNA
Cells
Embryonic Stem Cells
Nuclear Proteins
Cell Cycle Checkpoints
Small Interfering RNA
Cell Cycle
Stem Cells
Tissue

Keywords

  • Apoptosis
  • DNA damage
  • Hematopoietic stem cells
  • Nucleostemin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells. / Yamashita, Masayuki; Nitta, Eriko; Nagamatsu, Go; Ikushima, Yoshiko Matsumoto; Hosokawa, Kentaro; Arai, Fumio; Suda, Toshio.

In: Biochemical and Biophysical Research Communications, Vol. 441, No. 1, 08.11.2013, p. 196-201.

Research output: Contribution to journalArticle

Yamashita, Masayuki ; Nitta, Eriko ; Nagamatsu, Go ; Ikushima, Yoshiko Matsumoto ; Hosokawa, Kentaro ; Arai, Fumio ; Suda, Toshio. / Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 441, No. 1. pp. 196-201.
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