[HTML][HTML] Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells

HJ Snippert, LG Van Der Flier, T Sato, JH Van Es… - Cell, 2010 - cell.com
HJ Snippert, LG Van Der Flier, T Sato, JH Van Es, M Van Den Born, C Kroon-Veenboer…
Cell, 2010cell.com
Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at
the small intestinal crypt base and divide every day. We have carried out fate mapping of
individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5 hi stem
cells persist life-long, yet crypts drift toward clonality within a period of 1–6 months. We have
collected short-and long-term clonal tracing data of individual Lgr5 hi cells. These reveal that
most Lgr5 hi cell divisions occur symmetrically and do not support a model in which two …
Summary
Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5hi stem cells persist life-long, yet crypts drift toward clonality within a period of 1–6 months. We have collected short- and long-term clonal tracing data of individual Lgr5hi cells. These reveal that most Lgr5hi cell divisions occur symmetrically and do not support a model in which two daughter cells resulting from an Lgr5hi cell division adopt divergent fates (i.e., one Lgr5hi cell and one transit-amplifying [TA] cell per division). The cellular dynamics are consistent with a model in which the resident stem cells double their numbers each day and stochastically adopt stem or TA fates. Quantitative analysis shows that stem cell turnover follows a pattern of neutral drift dynamics.
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