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Publication : Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas.

First Author  Kozar S Year  2013
Journal  Cell Stem Cell Volume  13
Issue  5 Pages  626-33
PubMed ID  24035355 Mgi Jnum  J:202689
Mgi Id  MGI:5521235 Doi  10.1016/j.stem.2013.08.001
Citation  Kozar S, et al. (2013) Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Cell Stem Cell 13(5):626-33
abstractText  Lineage-tracing approaches, widely used to characterize stem cell populations, rely on the specificity and stability of individual markers for accurate results. We present a method in which genetic labeling in the intestinal epithelium is acquired as a mutation-induced clonal mark during DNA replication. By determining the rate of mutation in vivo and combining this data with the known neutral-drift dynamics that describe intestinal stem cell replacement, we quantify the number of functional stem cells in crypts and adenomas. Contrary to previous reports, we find that significantly lower numbers of "working" stem cells are present in the intestinal epithelium (five to seven per crypt) and in adenomas (nine per gland), and that those stem cells are also replaced at a significantly lower rate. These findings suggest that the bulk of tumor stem cell divisions serve only to replace stem cell loss, with rare clonal victors driving gland repopulation and tumor growth.
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