A Single Progenitor Population Switches Behavior to Maintain and Repair Esophageal Epithelium
Epithelial Defense Force
The nature of the cells that maintain and heal the epithelium lining the esophagus has been controversial. Doupéet al. (p. 1091, published online 19 July; see the Perspective by Kushner) show that, unlike many other tissues, mouse esophagus is devoid of slow cycling stem cells. Instead, the epithelium is maintained and repaired by a single population of proliferating cells that can switch rapidly from homeostatic behavior into “repair mode” in the vicinity of a wound.
Abstract
Diseases of the esophageal epithelium (EE), such as reflux esophagitis and cancer, are rising in incidence. Despite this, the cellular behaviors underlying EE homeostasis and repair remain controversial. Here, we show that in mice, EE is maintained by a single population of cells that divide stochastically to generate proliferating and differentiating daughters with equal probability. In response to challenge with all-trans retinoic acid (atRA), the balance of daughter cell fate is unaltered, but the rate of cell division increases. However, after wounding, cells reversibly switch to producing an excess of proliferating daughters until the wound has closed. Such fate-switching enables a single progenitor population to both maintain and repair tissue without the need for a “reserve” slow-cycling stem cell pool.
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Figs. S1 to S13
Table S1
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References and Notes
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Science
Volume 337 | Issue 6098
31 August 2012
31 August 2012
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Copyright © 2012, American Association for the Advancement of Science.
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Received: 6 January 2012
Accepted: 10 July 2012
Published in print: 31 August 2012
Acknowledgments
We thank E. Choolun and the staff at ARES and CBS Cambridge for technical assistance; D. Winton and D. Adams (Cambridge) for mice; and M. Gonzalez (London) for the Geminin antibody. We acknowledge the support of the MRC, EPSRC (Engineering and Physical Sciences Research Council), the NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research), the Wellcome Trust, Sidney Sussex College, Cambridge (D.P.D.), European Union Marie Curie Fellowship PIEF-LIF-2007-220016 (M.P.A.), the Royal College of Surgeons of England (A.R.), and Cambridge Cancer Centre (A.R.). This work uses methods included in the patent WO2009010725 (A2), a method of detecting altered behavior in a population of cells; inventors were P.H.J., B.D.S., and A.M.K.
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