
Intestinal crypt properties fit a model that incorporates replicative ageing and deep and proximate stem cells
Author(s) -
Lobachevsky P. N.,
Radford I. R.
Publication year - 2006
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2006.00395.x
Subject(s) - crypt , stem cell , biology , cell cycle , microbiology and biotechnology , small intestine , life span , adult stem cell , intestinal mucosa , ageing , cell , cellular differentiation , genetics , biochemistry , medicine , endocrinology , evolutionary biology , gene
. A model of intestinal crypt organization is suggested based on the assumption that stem cells have a finite replicative life span. The model assumes the existence in a crypt of a quiescent (‘deep’) stem cell and a few more actively cycling (‘proximate’) stem cells. Monte Carlo computer simulation of published intestinal crypt mutagenesis data is used to test the model. The results of the simulation indicate that stabilization of the crypt mutant phenotype following treatment with external mutagen is consistent with a stem cell replicative life span of about 40 divisions for mouse colon and 90–100 divisions for mouse small intestine, corresponding to a deep stem cell cycle time of about 3.9 and 8.5 weeks for colon and small intestine, respectively. Simulation of the data obtained for human colorectal crypts suggests that the proximate stem cell cycle time is about 80 h, assuming a replicative life span of 50–150 divisions, and that the deep stem cell divides approximately every 30 weeks.