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

Jing Wang, Fei Han, Juan Wu, Szu Wei Lee, Chia Hsin Chan, Ching Yuan Wu, Wei Lei Yang, Yuan Gao, Xian Zhang, Yun Seong Jeong, Asad Moten, Felipe Samaniego, Peng Huang, Quentin Liu, Yi Xin Zeng, Hui Kuan Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

50 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)5429-5438
Number of pages10
JournalBlood
Volume118
Issue number20
DOIs
StatePublished - 17 11 2011

Fingerprint

Dive into the research topics of 'The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal'. Together they form a unique fingerprint.

Cite this