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

TY - JOUR

T1 - Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells

AU - Snippert, H.J.G.

AU - van der Flier, L.G.

AU - Sato, T.

AU - van Es, J.H.

AU - van den Born, M.M.W.

AU - Kroon-Veenboer, C.

AU - Barker, N.

AU - Klein, A.M.

AU - van Rheenen, J.

AU - Simons, B.D.

AU - Clevers, H.

N1 - Reporting year: 2010 Metis note: S0092-8674(10)01064-0 [pii]

PY - 2010

Y1 - 2010

N2 - 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 daughter cells resulting from an Lgr5(hi) cell division adopt divergent fates (i.e., one Lgr5(hi) 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.

AB - 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 daughter cells resulting from an Lgr5(hi) cell division adopt divergent fates (i.e., one Lgr5(hi) 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.

U2 - 10.1016/j.cell.2010.09.016

DO - 10.1016/j.cell.2010.09.016

M3 - Article

SN - 0092-8674

VL - 143

SP - 134

EP - 144

JO - Cell

JF - Cell

IS - 1

ER -