title: Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells.
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 p16(Ink4a) or p19(Arf) deficiency. Taken together, our study demonstrates that nucleostemin protects HSCs from DNA damage accumulation and is required for the maintenance of HSCs.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan; Research Fellow of the Japan Society for the Promotion of Science, Kojimachi Business Center Building, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Eriko
authors.initials: E
authors.lastname: Nitta
authors.forename: Go
authors.initials: G
authors.lastname: Nagamatsu
authors.forename: Yoshiko Matsumoto
authors.initials: YM
authors.lastname: Ikushima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hosokawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Arai
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D003114:Colony-Forming Units Assay; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050764:Cyclin-Dependent Kinase Inhibitor p19 / Q000378:metabolism; D004249:DNA Damage; D019204:GTP-Binding Proteins; D042822:Genomic Instability; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C470311:nucleostemin protein, mouse; D019204:GTP-Binding Proteins
keywords: Apoptosis; DNA damage; Hematopoietic stem cells; Nucleostemin