# Stem Cell Dynamics in Colonic Epithelial Repair

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2020 · $18,211

## Abstract

PROJECT SUMMARY
The study of the regeneration of adult organs has undergone a major revolution with the discovery of specific
molecular markers of adult stem cells and development of techniques to grow organ-like structures outside the
body. In the mouse small intestine, the finding of multiple, distinctly marked populations of epithelial stem cells
has shaped our view of how self-renewing populations interact and are differentially utilized in physiological
contexts such as homeostasis and injury. Here we focus on stem cell populations in the mouse colon (large
intestine). The colonic epithelium is maintained by Lgr5-positive stem cells during normal tissue maintenance,
but the stem cell populations utilized in injury and their rules of interaction have not been elucidated. The
markers of injury-activated stem cell populations in the small intestine do not label stem cells in the colon. Our
goal is to characterize stem cell dynamics and signaling during mouse colonic epithelial repair states,
especially those that accompany or follow inflammatory injuries seen in human patients with inflammatory
bowel disease. This is possible in mouse colon because of the relative wealth of injury models and our recent
development of an imaging platform that allows stem cells to be visualized in the context of specialized tissue
repair structures over a large region. Preliminary data obtained for this application suggest that stem cell
population dynamics in repair are fundamentally different from those in homeostasis and that injury-induced
stem cells have a distinct molecular identity. These stem cells originate from both intestinal and squamous
tissues, and their repair dynamics result in a dramatic loss in clonal diversity. Specific aims for this project are:
(1) To analyze the cellular origins and dynamics of crypt regeneration in distal colon, (2) to determine the
origins and growth mechanisms of injury-induced squamous metaplasia in distal mouse colon, and (3) to
characterize the role of epidermal growth factor receptor (EGFR) signaling in stem cell responses to injury.
Primary methodologies used in our approach include lineage tracing, colonic organoid culture from mouse and
human tissue, high throughput sequencing, and utilization of advanced models of EGFR dysfunction. This work
will help identify specific cellular populations and processes to target for next generation therapies focusing on
the underutilized mucosal healing pathway in inflammatory bowel disease.

## Key facts

- **NIH application ID:** 9853780
- **Project number:** 5R01DK108648-05
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** D Brent Polk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $18,211
- **Award type:** 5
- **Project period:** 2016-02-01 → 2021-08-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853780

## Citation

> US National Institutes of Health, RePORTER application 9853780, Stem Cell Dynamics in Colonic Epithelial Repair (5R01DK108648-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853780. Licensed CC0.

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