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Tissue-Specific Stem Cells
Cyclin C Regulates Human Hematopoietic Stem/Progenitor Cell Quiescence†‡§
Article first published online: 4 DEC 2009
DOI: 10.1002/stem.270
Copyright © 2010 AlphaMed Press
Additional Information
How to Cite
Miyata, Y., Liu, Y., Jankovic, V., Sashida, G., Lee, J. M., Shieh, J.-H., Naoe, T., Moore, M. and Nimer, S. D. (2010), Cyclin C Regulates Human Hematopoietic Stem/Progenitor Cell Quiescence. STEM CELLS, 28: 308–317. doi: 10.1002/stem.270
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Author contributions: Y.M. and Y.L.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; V.J.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; G.S.: provision of study material or patients; J.M.L.: collection and/or assembly of data; J.-H.S. and T.N.: provision of study material or patients; M.M.: conception and design, data analysis and interpretation; S.D.N.: conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript.
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Disclosure of potential conflicts of interest is found at the end of this article.
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First published online in STEM CELLSEXPRESS January 28, 2010.
Publication History
- Issue published online: 16 FEB 2010
- Article first published online: 4 DEC 2009
- Accepted manuscript online: 4 DEC 2009 12:00AM EST
- Manuscript Accepted: 20 NOV 2009
- Manuscript Received: 28 JUL 2009
Funded by
- NIH R01. Grant Number: DK52208
- Leukemia and Lymphoma Society SCOR. Grant Number: 20790672
- Kitamura Hematology Foundation
Keywords:
- Cyclin C;
- Hematopoietic stem/progenitor cell;
- Human cord blood CD34+ cells;
- Quiescence;
- Engraftment
Abstract
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 G0 to the G1 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 G0/G1 transition of human HSPCs and suggest that modulating cyclin C levels may be useful for HSC expansion and more efficient engraftment. STEM CELLS 2010;28:308–317

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