Cell cycle heterogeneity in the small intestinal crypt and maintenance of genome integrity.
Stem Cells
; 28(7): 1250-9, 2010 Jul.
Article
in En
| MEDLINE
| ID: mdl-20503265
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Cycle
/
Genome
/
Intestine, Small
Limits:
Animals
Language:
En
Journal:
Stem Cells
Year:
2010
Type:
Article
Affiliation country:
United States