A single progenitor population switches behavior to maintain and repair esophageal epithelium

Science. 2012 Aug 31;337(6098):1091-3. doi: 10.1126/science.1218835. Epub 2012 Jul 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Doxycycline / pharmacology
  • Epithelial Cells / physiology*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Epithelium / physiology*
  • Esophagus / cytology*
  • Esophagus / physiology*
  • Green Fluorescent Proteins / biosynthesis
  • Histones / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / biosynthesis
  • Regeneration*
  • Stem Cells / metabolism
  • Stem Cells / physiology*

Substances

  • Biomarkers
  • Histones
  • Recombinant Fusion Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Doxycycline