Journal
EMBO JOURNAL
Volume 36, Issue 1, Pages 5-24Publisher
WILEY
DOI: 10.15252/embj.201694660
Keywords
epithelium; prostaglandin; restitution; stem cell; wound repair
Categories
Funding
- National Institutes of Health (NIH) [DK07161907]
- Crohn's and Colitis Foundation of America (CCFA) Genetics Initiative/Leona M. and Harry B. Helmsley Charitable Trust [274415]
- CCFA Research Fellowship Award [290895]
- K01 from NIH [DK109081]
- NCI [P30 CA91842]
- NIH National Center for Research Resources [UL1 TR000448]
- NIH Roadmap for Medical Research
Ask authors/readers for more resources
Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound-associated epithelial (WAE) cells form the initial barrier over the wound. Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our invitro primary epithelial cell culture system, we found that prostaglandin E2 (PGE(2)) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to invivo WAE cells. WAE cell differentiation was a permanent state and dominant over enterocyte differentiation in plasticity experiments. WAE cell differentiation was triggered by nuclear -catenin signaling independent of canonical Wnt signaling. Creation of WAE cells via the PGE(2)-Ptger4 pathway was required invivo, as mice with loss of Ptger4 in the intestinal epithelium did not produce WAE cells and exhibited impaired wound repair. Our results demonstrate a mechanism by which WAE cells are formed by PGE(2) and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available