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Updated: Oct 10, 2025
Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
Colonic healing requires Wnt produced by epithelium as well as Tagln+ and Acta2+ stromal cells
Soumyashree Das1, Qiang Feng1, Iyshwarya Balasubramanian1
1Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Abstract:
Although Wnt signaling is clearly important for the intestinal epithelial homeostasis, the relevance of various sources of Wnt ligands themselves remains incompletely understood. Blocking the release of Wnt in distinct stromal cell types suggests obligatory functions of several stromal cell sources and yields different observations. The physiological contribution of epithelial Wnt to tissue homeostasis remains unclear. We show here that blocking epithelial Wnts affects colonic Reg4+ epithelial cell differentiation and impairs colonic epithelial regeneration after injury in mice. Single-cell RNA analysis of intestinal stroma showed that the majority of Wnt-producing cells were contained in transgelin (Tagln+) and smooth muscle actin α2 (Acta2+) expressing populations. We genetically attenuated Wnt production from these stromal cells using Tagln-Cre and Acta2-CreER drivers, and found that blockage of Wnt release from either epithelium or Tagln+ and Acta2+ stromal cells impaired colonic epithelial healing after chemical-induced injury. Aggregated blockage of Wnt release from both epithelium and Tagln+ or Acta2+ stromal cells drastically diminished epithelial repair, increasing morbidity and mortality. These results from two uncharacterized stromal populations suggested that colonic recovery from colitis-like injury depends on multiple Wnt-producing sources.
Insights
Blocking epithelial Wnt impairs colonic regeneration, while Wnt from stromal cells is crucial for healing. Combined blockage severely hinders repair, highlighting multiple Wnt sources for intestinal homeostasis.
Area of Science:
- Gastroenterology and Hepatology
- Molecular Biology
- Cell Biology
Background:
- Wnt signaling is vital for intestinal epithelial homeostasis, but the specific roles of different Wnt ligand sources are not fully understood.
- Previous studies suggest distinct stromal cell types contribute to Wnt signaling, yet the epithelial contribution remains unclear.
Purpose of the Study:
- To investigate the physiological contribution of epithelial Wnt ligands to colonic tissue homeostasis and repair.
- To identify and characterize Wnt-producing stromal cell populations in the colon.
- To determine the collective importance of epithelial and stromal Wnt sources in colonic epithelial regeneration after injury.
Main Methods:
- Genetic manipulation to block Wnt release from specific epithelial and stromal cell populations in mice.
- Analysis of colonic epithelial cell differentiation and regeneration following chemical-induced injury.
- Single-cell RNA sequencing to identify Wnt-producing stromal cell populations (Tagln+ and Acta2+).
Main Results:
- Blocking epithelial Wnt impaired colonic Reg4+ epithelial cell differentiation and regeneration after injury.
- Single-cell RNA analysis identified transgelin (Tagln+) and smooth muscle actin α2 (Acta2+) expressing cells as major Wnt producers in the stroma.
- Genetic attenuation of Wnt production from Tagln+ or Acta2+ stromal cells, or the epithelium, impaired colonic healing.
- Combined blockage of Wnt release from both epithelium and these stromal populations drastically reduced epithelial repair, increasing morbidity and mortality.
Conclusions:
- Colonic epithelial regeneration after injury is dependent on Wnt ligands originating from multiple sources, including the epithelium and specific stromal populations (Tagln+ and Acta2+).
- The coordinated contribution of these diverse Wnt sources is essential for effective tissue repair and maintaining intestinal homeostasis.
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