# Intestinal stem cell control of regional secretory cell specialization

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $51,946

## Abstract

PROJECT SUMMARY
The intestine displays striking structural and functional variability along its length, allowing for
compartmentalization of distinct processes involved in absorption of nutrients and host defense. Regional
differences within the intestine are also evident in numerous gastrointestinal (GI) pathologies, such as ileocolitis
which is the most common forms of Crohn's disease, and necrotizing enterocolitis, both of which largely affect
the distal bowel. The underlying causes of regionality in these GI diseases and others are not well understood,
and therapies to restore structure and function to severely damaged or surgically resected diseased tissue are
critically needed. Specific subsets of secretory epithelial cells, which play critical roles in digestion and host
defense, vary in distribution across the length of the intestine, likely supporting localized functional demand
during homeostasis. Damage or disease, however, can radically alter the distributions of these cell types. For
example, hyperplasia of secretory tuft and goblet cells following parasite infection is a key component of the
tissue remodeling process that expels the pathogen. The cellular and molecular mechanisms that set the normal
distribution of secretory cells across the small intestine, and those that disturb secretory patterns in response to
parasite infection, are not known. Here, I will test the hypothesis that regional subpopulations of intestinal stem
cells (ISCs) that I have identified in my preliminary studies are programmed with a regional gene expression
signature termed regional identity (rID), that contributes to the specialized distribution of secretory cells across
the small intestine. To identify molecular mechanisms by which regional ISCs control secretory cell distribution
during homeostasis, I will analyze single cell RNA sequencing data to define rID transcripts relevant for the
control of secretory differentiation, and I will use genetic tools to manipulate these transcripts in ISCs in vitro. I
will then use microscopy and sequencing approaches to define cellular mechanisms that increase the relative
ratio of tuft and goblet cells in a parasite infection model. Collectively, these experiments will elucidate
mechanisms by which regional ISCs maintain specialized domains of secretory cells, and the relevance of this
organization for host defense against parasites, which represent one of the most common human infections in
the world. The results of this study have clinical implications for restoring regional function that has been
compromised by enteric infection, gastrointestinal disease, and bowel resection.

## Key facts

- **NIH application ID:** 9992991
- **Project number:** 1F32DK125089-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rachel Klapper Zwick
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $51,946
- **Award type:** 1
- **Project period:** 2020-03-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992991

## Citation

> US National Institutes of Health, RePORTER application 9992991, Intestinal stem cell control of regional secretory cell specialization (1F32DK125089-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9992991. Licensed CC0.

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