TY - JOUR
T1 - Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells
AU - Yamashita, Masayuki
AU - Nitta, Eriko
AU - Nagamatsu, Go
AU - Ikushima, Yoshiko Matsumoto
AU - Hosokawa, Kentaro
AU - Arai, Fumio
AU - Suda, Toshio
N1 - Funding Information:
We sincerely thank Dr. Tohru Minamino (Niigata University, Niigata, Japan) for providing the p53 flox/flox mice and Dr. Atsushi Hirao (Kanazawa University, Kanazawa, Japan) for providing the p16 Ink4a−/− p19 Arf−/− mice. We are grateful to the Collaborative Research Resources, School of Medicine, Keio University, for technical support and reagents. This work was supported by a Grant-in-Aid for Scientific Research and a Grant-in-Aid for Scientific Research on Innovative Areas “Cancer Stem Cells” from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and a Grant-in-Aid for Japan Society for the Promotion of Science Fellows.
PY - 2013/11/8
Y1 - 2013/11/8
N2 - 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.
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.
KW - Apoptosis
KW - DNA damage
KW - Hematopoietic stem cells
KW - Nucleostemin
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U2 - 10.1016/j.bbrc.2013.10.032
DO - 10.1016/j.bbrc.2013.10.032
M3 - Article
C2 - 24140061
AN - SCOPUS:84887445863
SN - 0006-291X
VL - 441
SP - 196
EP - 201
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -