Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells

被引：1475

作者：

Snippert, Hugo J. ^{[1
,2
]}

van der Flier, Laurens G. ^{[1
,2
]}

Sato, Toshiro ^{[1
,2
]}

van Es, Johan H. ^{[1
,2
]}

van den Born, Maaike ^{[1
,2
]}

Kroon-Veenboer, Carla ^{[1
,2
]}

Barker, Nick ^{[1
,2
]}

Klein, Allon M. ^{[3
,4
]}

van Rheenen, Jacco ^{[1
,2
]}

Simons, Benjamin D. ^{[4
]}

Clevers, Hans ^{[1
,2
]}

机构：

[1] KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[3] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[4] Univ Cambridge, Cavendish Lab, Dept Phys, Cambridge CB3 0HE, England

来源：

CELL | 2010年 / 143卷 / 01期

基金：

英国工程与自然科学研究理事会;

关键词：

MOUSE SMALL-INTESTINE; SELF-RENEWAL; HAIR FOLLICLE; BETA-CATENIN; IN-VITRO; DIFFERENTIATION; DIVISION; MARKER; GENE; IDENTIFICATION;

D O I：

10.1016/j.cell.2010.09.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：134 / 144

页数：11

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