# Study epigenetic inheritance during development, homeostasis and regeneration

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $399,556

## Abstract

Project Summary/Abstract:
Epigenetics refers to effects on gene expression or function that are inheritable through mitosis
or meiosis without altering the primary DNA sequences. Epigenetic mechanisms play important
roles in regulating cell identity and activity. Failure in appropriate epigenetic regulation leads to
abnormal behaviors of cells, which underlies many diseases such as diabetes, muscular
dystrophy, neurodegenerative disease, infertility, and many forms of cancer.
Many types of stem cells undergo asymmetric cell divisions to give rise to two daughter cells
with distinct cell fates: a self-renewed stem cell and to another daughter cell that differentiates.
We found that during the asymmetric division of Drosophila male germline stem cell (GSC), the
preexisting histones are selectively segregated to the GSC whereas newly synthesized histones
are enriched in the differentiating daughter cell. Our studies provide the first direct evidence that
stem cells retain preexisting histones during asymmetric cell divisions in vivo, which may
contribute to maintain their unique epigenetic memory.
In this proposal, we plan to: (1) explore what mechanisms control asymmetric versus symmetric
histone incorporation in Drosophila male germline; (2) study asymmetric histone inheritance and
its biological functions in Drosophila neuroblast and intestinal stem cell systems; (3) develop a
new method to identify genetic locus with epigenetic signature. We anticipate that our studies
will lead to (1) a series of findings to resolve fundamental questions in biology and yield new
insights in explaining cell fate determination in multicellular organisms, (2) the development of
new tools that will benefit the broader scientific community, and (3) insight on therapeutic
strategies against various diseases, such as degenerative disease and many forms of cancer, due
to mis-regulated cell fate determination.

## Key facts

- **NIH application ID:** 10842010
- **Project number:** 2R35GM127075-06
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xin Chen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,556
- **Award type:** 2
- **Project period:** 2018-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842010

## Citation

> US National Institutes of Health, RePORTER application 10842010, Study epigenetic inheritance during development, homeostasis and regeneration (2R35GM127075-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10842010. Licensed CC0.

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