Open AccessCyclin C Regulates Human Hematopoietic Stem/Progenitor Cell Quiescence
Author(s) -
Miyata Yasuhiko,
Liu Yan,
Jankovic Vladimir,
Sashida Goro,
Lee Jennifer May,
Shieh JaeHung,
Naoe Tomoki,
Moore Malcolm,
Nimer Stephen D.
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.270
Subject(s) - biology , microbiology and biotechnology , progenitor cell , stem cell , haematopoiesis , cd34 , cell cycle , cyclin , cyclin a , cyclin d , cancer research , cell , genetics
Hematopoietic stem cells (HSCs) can remain quiescent or they can enter the cell cycle, and either self‐renew or differentiate. Although cyclin C and cyclin dependent kinase (cdk3) are essential for the transition from the G 0 to the G 1 phase of the cell cycle in human fibroblasts, the role of cyclin C in hematopoietic stem/progenitor cells (HSPCs) is not clear. We have identified an important role of cyclin C (CCNC) in regulating human HSPC quiescence, as knocking down CCNC expression in human cord blood CD34 + cells resulted in a significant increase in quiescent cells that maintain CD34 expression. CCNC knockdown also promotes in vitro HSPC expansion and enhances their engraftment potential in sublethally irradiated immunodeficient mice. Our studies establish cyclin C as a critical regulator of the G 0 /G 1 transition of human HSPCs and suggest that modulating cyclin C levels may be useful for HSC expansion and more efficient engraftment. S TEM C ELLS 2010;28:308–317