# Colonic epithelial wound healing by anal transitional cells

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $564,004

## Abstract

PROJECT SUMMARY
Mucosal healing is the primary goal of all therapies for inflammatory bowel disease (IBD). No currently
approved therapy directly promotes wound healing of the bowel epithelium, which forms a single-cell barrier
between the host and lumen and regulates the immune response. The cellular and molecular mechanisms that
define the healing process remain to be defined. The intestinal crypt maintains the normal turnover of epithelial
cells within a vertical lineage hierarchy of basal stem and terminally differentiated luminal cells. During wound
healing, this lineage hierarchy is suspended, and epithelial cells can undergo dedifferentiation to mediate re-
epithelialization. In recent work, we have identified an alternate source of wound healing in the distal colon of
mice. In acute and chronic models of colitis, a skin-like cell population at the anal transition zone (ATZ),
bordering the sharp squamocolumnar anorectal junction, migrates into the colon and forms a permanent hybrid
epithelial structure called squamous neo-epithelium of colon (SNEC). SNEC represents the end-product of
wound healing by cells of the ATZ. The ATZ is an anatomically small region that is composed of a unique
population of epithelial stem cells that have a mixed colonic/epidermal phenotype and are capable of wound-
healing plasticity. Moreover, these stem cells are partially resistant to the damage of colitis. The study of these
cells could highlight new pathways for colonic epithelial regeneration in the context of IBD. However, the
lineage diversity and relationships within the myriad tissue types of the human ATZ are not known, and
furthermore it remains to be defined whether ATZ stem cells might provide enduring intestinal function, protect
from potential oncogenic sequela, or repair ulcers throughout the colon. In the proposed work, we will test
whether ATZ-derived stem cells could be suitable reagents to mediate colonic epithelial wound healing and
identify key pathways that contribute to their proliferative potential. The Specific Aims of the project are: 1) to
define regenerative cell populations in the human ATZ, 2) to define long-term outcomes of endogenous colonic
wound healing by ATZ cells, and 3) to identify mechanisms of functional ATZ plasticity in wound healing. A
deeper investigation of the mechanisms, implications, and potential translation of this noncanonical form of
colonic wound healing could reveal new therapeutic targets to direct mucosal healing in IBD.

## Key facts

- **NIH application ID:** 10637886
- **Project number:** 1R01DK135954-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Cambrian Yangshao Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $564,004
- **Award type:** 1
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10637886

## Citation

> US National Institutes of Health, RePORTER application 10637886, Colonic epithelial wound healing by anal transitional cells (1R01DK135954-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10637886. Licensed CC0.

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