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 journalArticle

1045 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)134-144
Number of pages11
JournalCell
Volume143
Issue number1
DOIs
Publication statusPublished - 2010 Oct
Externally publishedYes

Keywords

  • Devbio
  • Stemcell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., & Clevers, H. (2010). Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell, 143(1), 134-144. https://doi.org/10.1016/j.cell.2010.09.016