# Interrogating sub-epithelial cell heterogeneity in the developing human intestinal stem cell niche

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $74,284

## Abstract

Project Abstract
Maintenance and regeneration of various organs is dependent upon specialized stem cell populations. These
populations require highly specific environments and external cues to maintain their multipotent capabilities or
specifically trigger expansion and differentiation resulting in growth and development or repairing of the organ
after damage. The advent of stem cell derived enteroid and organoid culture models has given insight into the
signaling requirements of many stem cell populations and allowed for intensive study of the necessary niche
signals that direct behavior.
Previous data has suggested a role for sub-epithelial cells (SECs) in maintaining the intestinal stem cell niche.
Our lab recently described an SEC population in the developing human intestine defined by the unique
expression of F3 and PDGFRA (F3+/PDGFRAhi). This population, which lines the entire crypt-villus axis, can
be further divided by NPY expression into villus localized (NPY+) and crypt localized (NPY-) populations using
both single cell RNA sequencing (scRNAseq) and fluorescent in situ hybridization (FiSH). My preliminary data
has compared single cell RNA-sequencing (scRNA-seq) data and identified differentially expressed genes in
villus-SECs and crypt-SECs, including secreted proteins and receptors, identifying putative novel intestinal
niche factors.
One of the putative niche factors that my analysis identified was HGF (Hepatocyte Growth Factor), which was
enriched in the crypt-base SECs. The HGF receptor c-MET was found to be localized to the intestinal
epithelium in both mouse and human scRNA-seq datasets during fetal development. HGF is well known for its
roles in development, wound healing/regeneration, and cancer in many tissues including the intestinal
epithelium.
My proposal is designed to test the hypothesis that the crypt-based SECs have intestinal niche supporting
function through HGF signaling we will 1) characterize the distinct SEC sup-populations and 2) determine if
HGF is necessary and sufficient to support human intestinal stem cell growth and development in induced
pluripotent stem cell-derived human intestinal organoids (iPSC-HIOs). After HIO survival in media
supplemented with HGF is confirmed, the HIO cultures both before and after transplantation beneath a mouse
kidney capsule will be analyzed to define any differences between the EGF-HIOs and HGF-HIOs.

## Key facts

- **NIH application ID:** 10821630
- **Project number:** 1F32DK138694-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kelli Johnson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2023-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821630

## Citation

> US National Institutes of Health, RePORTER application 10821630, Interrogating sub-epithelial cell heterogeneity in the developing human intestinal stem cell niche (1F32DK138694-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10821630. Licensed CC0.

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