TY - JOUR
T1 - Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells
AU - Snippert, Hugo J.
AU - van der Flier, Laurens G.
AU - Sato, Toshiro
AU - van Es, Johan H.
AU - van den Born, Maaike
AU - Kroon-Veenboer, Carla
AU - Barker, Nick
AU - Klein, Allon M.
AU - van Rheenen, Jacco
AU - Simons, Benjamin D.
AU - Clevers, Hans
PY - 2010/10
Y1 - 2010/10
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, 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.
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, 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.
KW - Devbio
KW - Stemcell
UR - http://www.scopus.com/inward/record.url?scp=77957223906&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957223906&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2010.09.016
DO - 10.1016/j.cell.2010.09.016
M3 - Article
C2 - 20887898
AN - SCOPUS:77957223906
SN - 0092-8674
VL - 143
SP - 134
EP - 144
JO - Cell
JF - Cell
IS - 1
ER -