Brief report: Dclk1 deletion in tuft cells results in impaired epithelial repair after radiation injury

Stem Cells. 2014 Mar;32(3):822-7. doi: 10.1002/stem.1566.

Abstract

The role of Dclk1(+) tuft cells in the replacement of intestinal epithelia and reestablishing the epithelial barrier after severe genotoxic insult is completely unknown. Successful restoration requires precise coordination between the cells within each crypt subunit. While the mechanisms that control this response remain largely uncertain, the radiation model remains an exceptional surrogate for stem cell-associated crypt loss. Following the creation of Dclk1-intestinal-epithelial-deficient Villin-Cre;Dclk1(flox/flox) mice, widespread gene expression changes were detected in isolated intestinal epithelia during homeostasis. While the number of surviving crypts was unaffected, Villin-Cre;Dclk1(flox/flox) mice failed to maintain tight junctions and died at approximately 5 days, where Dclk1(flox/flox) mice lived until day 10 following radiation injury. These findings suggest that Dclk1 plays a functional role critical in the epithelial restorative response.

Keywords: Conditional knockout; Cre-loxP system; Irradiation; Notch; Stem cell-microenvironment interactions; Tissue regeneration; Tissue-specific stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology*
  • Gene Deletion*
  • Gene Expression Regulation
  • Intestinal Mucosa / pathology*
  • Mice
  • Protein-Serine-Threonine Kinases / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation Injuries / metabolism
  • Radiation Injuries / pathology*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Survival Analysis
  • Whole-Body Irradiation
  • Wound Healing*

Substances

  • RNA, Messenger
  • Receptors, Notch
  • Dcamkl1 protein, mouse
  • Protein-Serine-Threonine Kinases