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

研究成果: Article査読

1434 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)134-144
ページ数11
ジャーナルCell
143
1
DOI
出版ステータスPublished - 2010 10月
外部発表はい

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学一般

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