Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells.
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.
Snippert
Hugo J
HJ
Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
van der Flier
Laurens G
LG
Sato
Toshiro
T
van Es
Johan H
JH
van den Born
Maaike
M
Kroon-Veenboer
Carla
C
Barker
Nick
N
Klein
Allon M
AM
van Rheenen
Jacco
J
Simons
Benjamin D
BD
Clevers
Hans
H
D000818:Animals; D019070:Cell Lineage; D002999:Clone Cells; D007421:Intestine, Small / Q000166:cytology*; D051379:Mice; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled