# Characterization of age-related changes in spermatogonial dedifferentiation

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $254,250

## Abstract

Project Summary
The broad, long-term objectives of this application are to characterize how age-related intrinsic changes in gene
expression and age-related extrinsic changes in the niche microenvironment impact the process of
dedifferentiation. This proposal will examine these issues using spermatogonial dedifferentiation - in which
differentiating germ cells revert to become spermatogonial stem cells - in the Drosophila testis. State of the art
techniques will be used to detect genome-wide binding of RNA Polymerase II in dedifferentiating spermatogonia.
The proposal will capitalize upon the powerful genetics and lineage tracing available in Drosophila, as well as
the ability to unequivocally identify the niche, spermatogonial stem cells, spermatogonia and somatic support
cells in the Drosophila testis. This proposal is supported by published results demonstrating that spermatogonial
dedifferentiation is required to maintain a robust pool of spermatogonial stem cells over a lifetime and that this
process requires Jun N-terminal kinase (JNK) signaling. This work is also supported by unpublished preliminary
data showing that the rate of spermatogonial dedifferentiation declines steeply during aging. Additionally, this
proposal is supported by unpublished results showing that the niche microenvironment changes substantially
during aging: in old males, an ectopic extracellular matrix accumulates around the niche. In the first aim, targeted
DamID will be used to obtain the genome-wide binding of RNA Pol II only in reverting spermatogonia in testes
from young and old males. Analyses of these data sets will reveal genes that are activated in young but not old
spermatogonia. In the second aim, one or two validated genes from Aim 1 will be used to test the model that
candidate gene depletion in young testes should decrease dedifferentiation rates and its overexpression should
increase reversion rates in old males. Experiments in the second aim will also test the hypothesis that decreased
dedifferentiation in old males is a result of reverting cells not upregulating extracellular matrix-binding proteins.
The studies in this proposal will increase the knowledge base about how aging affects dedifferentiation in more
complex system and will foster new avenues of research into mechanisms and treatments for age-related male
infertility.

## Key facts

- **NIH application ID:** 10215936
- **Project number:** 1R21AG068103-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Erika A Bach
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2021-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215936

## Citation

> US National Institutes of Health, RePORTER application 10215936, Characterization of age-related changes in spermatogonial dedifferentiation (1R21AG068103-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10215936. Licensed CC0.

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