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

Hugo J. Snippert; Laurens G. van der Flier; Toshiro Sato; Johan H. van Es; Maaike van den Born; Carla Kroon-Veenboer; Nick Barker; Allon M. Klein; Jacco van Rheenen; Benjamin D. Simons; Hans Clevers

doi:10.1016/j.cell.2010.09.016

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

Hugo J. Snippert, Laurens G. van der Flier, Toshiro Sato, Johan H. van Es, Maaike van den Born, Carla Kroon-Veenboer, Nick Barker, Allon M. Klein, Jacco van Rheenen, Benjamin D. Simons, Hans Clevers

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	134-144
Number of pages	11
Journal	Cell
Volume	143
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2010.09.016
Publication status	Published - Oct 2010
Externally published	Yes

Keywords

Devbio
Stemcell

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title = "Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells",

abstract = "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.",

keywords = "Devbio, Stemcell",

author = "Snippert, {Hugo J.} and {van der Flier}, {Laurens G.} and Toshiro Sato and {van Es}, {Johan H.} and {van den Born}, Maaike and Carla Kroon-Veenboer and Nick Barker and Klein, {Allon M.} and {van Rheenen}, Jacco and Simons, {Benjamin D.} and Hans Clevers",

year = "2010",

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doi = "10.1016/j.cell.2010.09.016",

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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.

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SN - 0092-8674

VL - 143

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JO - Cell

JF - Cell

IS - 1

ER -

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

Abstract

Keywords

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