# Intestinal Niche in Homeostasis and Epithelial Regeneration

> **NIH NIH U01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $397,032

## Abstract

Project Summary
The intestinal epithelium exhibits a remarkable capacity of self-renewal which reflects the activity of multi-
potent intestinal stem cells (ISCs) that divide and differentiate to produce the different cell types that comprise
the intestinal epithelium. Control of ISC activity is thought to be mediated by factors produced by other cells
that reside either in the stromal layer surrounding the intestinal crypt, by cells in the adjoining epithelium, and
by the microbiome that resides in the small intestinal lumen. These factors create an environment called the
“stem cell niche”. Our past work and preliminary findings indicate that epithelial WNTs, stromal myofibroblasts
and monocytes, and commensal derived factors are all components of the ISC niche. This renewal application
seeks support to continue to collaborate in the Intestinal Stem Cell Consortium (ISCC) to extend our previous
work defining the role of epithelial, stromal, and luminal intestinal factors that regulate ISC proliferation to
acquire knowledge to regenerate and rebuild the human intestine. Gaining a molecular understanding of the
role that these cells and factors play in the niche will be essential to consider when building intestine. Our
proposed studies within the goals of the ISCC are follows: Goal 1: define essential niche components that
contribute to intestinal epithelial homeostasis by (a) determining what microbial communities inhabit the human
intestinal crypt and what their role is in regulating the ISC and (b) evaluating how intestinal myofibroblasts and
monocytes affect proliferation and lineage differentiation of ISCs. Goal 2: determine niche components that
are altered following injury and evaluate whether they play a role in epithelial regeneration by (a) dissecting
the molecular signaling pathways in damaged epithelium that stimulate the ISC through WNT3, and (b)
determining the specific role of human WNT2B in ISC–induced regeneration. The mission of the ISCC is to
characterize the minimal, required niche cells and factors that support ISC in health and disease, using an
integrated, multidisciplinary team science approach. Our proposed research complements and synergizes with
the other eight projects of the ISCC to achieve the ultimate goal of developing both humoral and tissue therapy
for gastrointestinal diseases via modulation of factors that comprise the ISC niche. Combining and sharing our
skills and resources will allow rapid advancement of ISC biology and application of new knowledge to repair
and build an intestine.

## Key facts

- **NIH application ID:** 10229384
- **Project number:** 5U01DK103168-08
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mary Kolb Estes
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,032
- **Award type:** 5
- **Project period:** 2014-09-05 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229384

## Citation

> US National Institutes of Health, RePORTER application 10229384, Intestinal Niche in Homeostasis and Epithelial Regeneration (5U01DK103168-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10229384. Licensed CC0.

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