# Determining the role of Tet1 in intestinal stem cell differentiation and self-renewal

> **NIH NIH R03** · EMORY UNIVERSITY · 2020 · $117,000

## Abstract

ABSTRACT
Intestinal stem cells (ISCs) reside in intestinal crypts and undergo continual proliferation, self-renewal, and
differentiation in order to maintain function of the intestinal epithelium, which is replaced approximately once a
week throughout adult life. Precise regulation of cell fate decisions between self-renewal and differentiation is
critical for ISC homeostasis and damage response, but the role of chromatin regulation in balancing these
decisions remains poorly characterized. Our currently funded K01 focuses on dissecting the genomic
regulatory network of Tet1, which catalyzes DNA demethylation and is specifically enriched in ISC populations.
Preliminary data from these studies demonstrate that loss of Tet1 results in remarkably rapid crypt hyperplasia
and increased ISC function, which occurs within 5 days of Tet1 ablation. The central hypothesis of the
proposed study is that Tet1 negatively regulates ISC activity by promoting differentiation. To test this
hypothesis and expand on our K01, we will: (1) characterize the phenotypic role of Tet1 in ISC proliferation and
differentiation in vivo, at 5 days and 4 weeks post-ablation (Aim 1) and (2) map the Tet1-dependent genomic
landscape of 5-hydroxymethylcytosine (5hmC), the primary product of TET1 catalytic activity, in ISCs,
progenitors, and post-mitotic cells (Aim 2). Collectively, these Aims will expand on and integrate with our
ongoing K01 studies to provide sufficient preliminary data for future, R01-funded investigation of Tet1-mediated
mechanisms involved in ISC homeostasis and regeneration.

## Key facts

- **NIH application ID:** 10193967
- **Project number:** 7R03DK122111-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Adam David Gracz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $117,000
- **Award type:** 7
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10193967

## Citation

> US National Institutes of Health, RePORTER application 10193967, Determining the role of Tet1 in intestinal stem cell differentiation and self-renewal (7R03DK122111-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10193967. Licensed CC0.

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