# Chromatin modifier Polycomb Repressive Complex 2 as a regulator of dental epithelial progenitor cells

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $54,774

## Abstract

Project Summary/Abstract
Understanding the mechanisms of dental epithelial progenitor cell fate decisions will help to lay the long-term
groundwork for clinical applications of stem cell biology in human dentition. In the continuously growing mouse
incisor, cycling progenitor cells orchestrate incisor epithelium renewal during both homeostasis and injury-
induced regeneration. The swift and well-orchestrated balance of progenitor cell self-renewal and differentiation
into either enamel-producing ameloblasts or non-ameloblasts supports the continuous growth of the tooth.
However, the mechanisms that control these rapid fate decisions remain unclear. To understand mechanisms
of cell fate decisions, this proposal will examine how Polycomb Repressive Complex 2 (PRC2), through
trimethylation of lysine 27 on Histone 3, represses gene expression to drive fate commitment of progenitor cells.
This proposal will establish the role of PRC2 catalytic subunit Enhancer of Zeste Homolog 2 (EZH2) in the incisor
epithelium and its specific chromatin targets during progenitor differentiation. Aim 1 will examine how EZH2
contributes to incisor epithelial progenitor cell fate decisions during homeostasis and injury-induced
regeneration. This will be achieved by determining how loss of Ezh2 in progenitor cells affects cell fate decisions,
such as changes to differentiation, self-renewal or apoptosis. Aim 2 will elucidate the specific targets of EZH2
in progenitor cells during homeostasis and injury-induced regeneration. Chromatin states of incisor
epithelial cells during both conditions will be determined using state-of-the-art single-cell Assay for Transposase
Accessible Chromatin sequencing (scATACseq) and Cleavage Under Targets and Release Using Nuclease
(CUT&RUN) technologies. These analyses will show whether PRC2 targets in the incisor epithelium are similar
to those in other self-renewing tissues. They will also identify the dental epithelial tissue-specific targets that
contribute to ameloblast and non-ameloblast fates.
This research plan will be conducted in conjunction with a comprehensive training plan designed to develop the
applicant’s career as a dentist-scientist. The training includes structured mentorship from a highly qualified
clinician-scientist sponsor, as well as scientific and technical training through attending seminars, journal clubs,
classes, laboratory meetings, conferences, and more. Research and training will take place at the University of
California, San Francisco, which offers both an outstanding research environment and an excellent dental school
for clinical training.

## Key facts

- **NIH application ID:** 10883610
- **Project number:** 5F30DE032265-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David Sung
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,774
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883610

## Citation

> US National Institutes of Health, RePORTER application 10883610, Chromatin modifier Polycomb Repressive Complex 2 as a regulator of dental epithelial progenitor cells (5F30DE032265-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10883610. Licensed CC0.

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