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Tissue-Specific Stem Cells
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Cell Cycle Heterogeneity in the Small Intestinal Crypt and Maintenance of Genome Integrity†‡§
Article first published online: 25 MAY 2010
DOI: 10.1002/stem.450
Copyright © 2010 AlphaMed Press
Additional Information
How to Cite
Pruitt, S. C., Freeland, A. and Kudla, A. (2010), Cell Cycle Heterogeneity in the Small Intestinal Crypt and Maintenance of Genome Integrity. STEM CELLS, 28: 1250–1259. doi: 10.1002/stem.450
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Author contributions: S.C.P.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; A.F.: collection and/or assembly of data; A.K.: collection and/or assembly of data.
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First published online in STEM CELLSEXPRESS May 25, 2010.
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Disclosure of potential conflicts of interest is found at the end of this article.
Publication History
- Issue published online: 20 JUL 2010
- Article first published online: 25 MAY 2010
- Manuscript Accepted: 13 MAY 2010
- Manuscript Received: 29 JAN 2010
Funded by
- NIH. Grant Number: CA130995
- Ellison Medical Foundation Senior Scholar award
- Comprehensive Cancer Center Support Grant. Grant Number: CA016056
Keywords:
- Intestinal stem cells;
- Mini-chromosome maintenance 2;
- Replication licensing factor;
- Somatic selection;
- Quiescence;
- DNA damage response
Abstract
Stem cell quiescence has been hypothesized to suppress the rate at which genetic mutations accumulate within tissues by reducing the number of divisions a cell undergoes. However, recent studies have suggested that stem cells in the small intestine are rapidly dividing. This observation raises the issue of whether replication related errors are an important contributor to the accumulation of genetic damage and, if so, how genomic integrity is maintained within the small intestine. Here, reporter-marked small intestinal epithelial cells, resulting from mini-chromosome maintenance protein 2 (Mcm2) gene driven Cre-mediated recombination, are shown to be retained at the +1 position within the crypt and to contribute to the intestinal epithelia over long periods. Additionally, we show that the rate of cycling of +1 position Mcm2-expressing stem cells is heterogeneous with cycling times ranging between 1 and 4 days. Further, this heterogeneity depends on the p53 signaling pathway and could provide the basis for retention and expansion, through niche succession and crypt fission, of genetically intact stem cells. This somatic selection process would require active cellular replication. STEM CELLS 2010;28:1250–1259