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The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal

Publication ,  Journal Article
Wang, J; Han, F; Wu, J; Lee, S-W; Chan, C-H; Wu, C-Y; Yang, W-L; Gao, Y; Zhang, X; Jeong, YS; Moten, A; Samaniego, F; Huang, P; Liu, Q ...
Published in: Blood
November 17, 2011

Although the maintenance of HSC quiescence and self-renewal are critical for controlling stem cell pool and transplantation efficiency, the mechanisms by which they are regulated remain largely unknown. Understanding the factors controlling these processes may have important therapeutic potential for BM failure and cancers. Here, we show that Skp2, a component of the Skp2 SCF complex, is an important regulator for HSC quiescence, frequency, and self-renewal capability. Skp2 deficiency displays a marked enhancement of HSC populations through promoting cell cycle entry independently of its role on apoptosis. Surprisingly, Skp2 deficiency in HSCs reduces quiescence and displays increased HSC cycling and proliferation. Importantly, loss of Skp2 not only increases HSC populations and long-term reconstitution ability but also rescues the defect in long-term reconstitution ability of HSCs on PTEN inactivation. Mechanistically, we show that Skp2 deficiency induces Cyclin D1 gene expression, which contributes to an increase in HSC cycling. Finally, we demonstrate that Skp2 deficiency enhances sensitivity of Lin− Sca-1+ c-kit+ cells and leukemia cells to chemotherapy agents. Our findings show that Skp2 is a novel regulator for HSC quiescence and self-renewal and that targeting Skp2 may have therapeutic implications for BM transplantation and leukemia stem cell treatment.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 17, 2011

Volume

118

Issue

20

Start / End Page

5429 / 5438

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, J., Han, F., Wu, J., Lee, S.-W., Chan, C.-H., Wu, C.-Y., … Lin, H.-K. (2011). The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal. Blood, 118(20), 5429–5438. https://doi.org/10.1182/blood-2010-10-312785
Wang, Jing, Fei Han, Juan Wu, Szu-Wei Lee, Chia-Hsin Chan, Ching-Yuan Wu, Wei-Lei Yang, et al. “The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal.” Blood 118, no. 20 (November 17, 2011): 5429–38. https://doi.org/10.1182/blood-2010-10-312785.
Wang J, Han F, Wu J, Lee S-W, Chan C-H, Wu C-Y, et al. The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal. Blood. 2011 Nov 17;118(20):5429–38.
Wang, Jing, et al. “The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal.” Blood, vol. 118, no. 20, American Society of Hematology, Nov. 2011, pp. 5429–38. Crossref, doi:10.1182/blood-2010-10-312785.
Wang J, Han F, Wu J, Lee S-W, Chan C-H, Wu C-Y, Yang W-L, Gao Y, Zhang X, Jeong YS, Moten A, Samaniego F, Huang P, Liu Q, Zeng Y-X, Lin H-K. The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal. Blood. American Society of Hematology; 2011 Nov 17;118(20):5429–5438.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 17, 2011

Volume

118

Issue

20

Start / End Page

5429 / 5438

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology