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

研究成果: Article

16 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)196-201
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
441
発行部数1
DOI
出版物ステータスPublished - 2013 11 8

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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

ASJC Scopus subject areas

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

これを引用

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.

:: Biochemical and Biophysical Research Communications, 巻 441, 番号 1, 08.11.2013, p. 196-201.

研究成果: Article

Yamashita, M, Nitta, E, Nagamatsu, G, Ikushima, YM, Hosokawa, K, Arai, F & Suda, T 2013, 'Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells', Biochemical and Biophysical Research Communications, 巻. 441, 番号 1, pp. 196-201. https://doi.org/10.1016/j.bbrc.2013.10.032
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. :: Biochemical and Biophysical Research Communications. 2013 ; 巻 441, 番号 1. pp. 196-201.
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AU - Hosokawa, Kentaro

AU - Arai, Fumio

AU - Suda, Toshio

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AB - 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.

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