Cyclin C regulates human hematopoietic stem/progenitor cell quiescence.
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.
Miyata
Yasuhiko
Y
Molecular Pharmacology and Chemistry Program and Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Liu
Yan
Y
Jankovic
Vladimir
V
Sashida
Goro
G
Lee
Jennifer May
JM
Shieh
Jae-Hung
JH
Naoe
Tomoki
T
Moore
Malcolm
M
Nimer
Stephen D
SD
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D056745:Cyclin C / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology
D018952:Antigens, CD34; D056745:Cyclin C; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering