Stem cell self-renewal in intestinal crypt.

As a rapidly cycling tissue capable of fast repair and regeneration, the intestinal epithelium has emerged as a favored model system to explore the principles of adult stem cell biology. However, until recently, the identity and characteristics of the stem cell population in both the small intestine and colon has remained the subject of debate. Recent studies based on targeted lineage tracing strategies, combined with the development of an organotypic culture system, have identified the crypt base columnar cell as the intestinal stem cell, and have unveiled the strategy by which the balance between proliferation and differentiation is maintained. These results show that intestinal stem cells operate in a dynamic environment in which frequent and stochastic stem cell loss is compensated by the proliferation of neighboring stem cells. We review the basis of these experimental findings and the insights they offer into the mechanisms of homeostatic stem cell regulation.

[1]  Hans Clevers,et al.  Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells , 2010, Cell.

[2]  G. Williams,et al.  Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry , 1988, Nature.

[3]  M. Bjerknes,et al.  Multipotential stem cells in adult mouse gastric epithelium. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[4]  Hans Clevers,et al.  Transcription Factor Achaete Scute-Like 2 Controls Intestinal Stem Cell Fate , 2009, Cell.

[5]  F M Watt,et al.  Out of Eden: stem cells and their niches. , 2000, Science.

[6]  T. Graham,et al.  Use of methylation patterns to determine expansion of stem cell clones in human colon tissue. , 2011, Gastroenterology.

[7]  D. Winton,et al.  Stem-cell organization in mouse small intestine , 1990, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[8]  H. Clevers,et al.  Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. , 2009, Gastroenterology.

[9]  Peter M. Lansdorp,et al.  Identification of sister chromatids by DNA template strand sequences , 2010, Nature.

[10]  A. Cairnie,et al.  Cell proliferation studies in the intestinal epithelium of the rat. II. Theoretical aspects. , 1965, Experimental cell research.

[11]  C. P. Leblond,et al.  Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. , 1974, The American journal of anatomy.

[12]  H. Clevers,et al.  Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes , 2011, The EMBO journal.

[13]  C. P. Leblond,et al.  The constant renewal of the intestinal epithelium in the albino rat , 1948, The Anatomical record.

[14]  H Cheng,et al.  The stem-cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse. , 1981, The American journal of anatomy.

[15]  H. Clevers,et al.  Identification of stem cells in small intestine and colon by marker gene Lgr5 , 2007, Nature.

[16]  Hans Clevers,et al.  Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue. , 2010, Cell stem cell.

[17]  Simon Tavaré,et al.  The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns , 2007, PLoS Comput. Biol..

[18]  B. A. J. Ponder,et al.  A clonal marker induced by mutation in mouse intestinal epithelium , 1988, Nature.

[19]  Allon M Klein,et al.  Intestinal Stem Cell Replacement Follows a Pattern of Neutral Drift , 2010, Science.

[20]  R. Richardson,et al.  Prominin1 marks intestinal stem cells that are susceptible to neoplastic transformation , 2008, Nature.

[21]  T. Tumbar,et al.  Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells. , 2009, Cell stem cell.

[22]  Benjamin D. Simons,et al.  A single type of progenitor cell maintains normal epidermis , 2007, Nature.

[23]  N. Wright Epithelial stem cell repertoire in the gut: clues to the origin of cell lineages, proliferative units and cancer , 2000, International journal of experimental pathology.

[24]  H. Clevers,et al.  Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche , 2009, Nature.

[25]  Camilla A. Richmond,et al.  Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells , 2010, Proceedings of the National Academy of Sciences.

[26]  Allon M. Klein,et al.  Universal patterns of stem cell fate in cycling adult tissues , 2011, Development.

[27]  Nicholas A. Wright,et al.  The biology of epithelial cell populations , 1984 .

[28]  Hans Clevers,et al.  Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts , 2011, Nature.

[29]  L. Lajtha Stem cell concepts. , 1979, Nouvelle revue francaise d'hematologie.

[30]  Allon M. Klein,et al.  Mouse germ line stem cells undergo rapid and stochastic turnover. , 2010, Cell stem cell.

[31]  C. Potten,et al.  CONTINUOUS LABELLING STUDIES ON MOUSE SKIN AND INTESTINE , 1974, Cell and tissue kinetics.