# Regulation of Male Germ Cell Development through DND1-Mediated Translation of Epigenetic Factors

> **NIH NIH F32** · DUKE UNIVERSITY · 2024 · $62,269

## Abstract

PROJECT SUMMARY
Male germ cells (MGCs) are precursors to spermatogonial stem cells (SSCs), a stem cell population that both
self-renews and differentiates, supplying spermatozoa for the entirety of a male’s reproductive lifespan.
Disruptions in development of MGCs during fetal life leads to infertility in humans and mice. Just prior to birth,
MGCs undergo a relatively long period of cellular quiescence. This G0 arrest phase is conserved between mice
and humans and is considered an MGC reprogramming stage. During this time, MGCs lose their early GC fate
and acquire the molecular profile of SSCs by undergoing vast epigenetic modifications. Although increases in
mRNA levels of various epigenetic factors occur during G0, it is unclear how the transcripts of epigenetic factors
are regulated post-transcriptionally throughout G0. DND1 is one of many RNA-binding proteins (RBPs) required
for MGC development, and it is essential for both G0 arrest and for RNA expression of epigenetic regulators
during G0. Transcript targets of DND1 during G0 include vital epigenetic regulators. Functionally, DND1 can
promote transcript degradation, protect transcripts from degradation, or promote their translation. Because DND1
has multiple regulatory roles, it is unknown how DND1 post-transcriptionally regulates its target transcripts during
G0 to ensure MGC-to-SSC development. In this proposal, how transcripts of epigenetic factors are post-
transcriptionally regulated G0 in MGCs will be determined by focusing on the translational role of DND1, as
supported by preliminary data. The central hypothesis is that an essential role of DND1 is to control when
and where its target epigenetic regulators are translated during G0 to direct the reprogramming of MGCs
into SSCs. To test this hypothesis, in Aim 1, DND1-bound transcripts that encode for epigenetic regulators and
that are translated during G0 will be defined. The proteomes will be determined through LC/MS-TOF in two
stages of G0 and will be cross-referenced to previously obtained DND1-target transcripts at their respective
stages, creating DND1-directed translatomes. Epigenetic regulators in these translatomes will be assessed for
nascent translation throughout G0 to determine their temporal translational regulation. In Aim 2, it will be
determined where and how DND1 promotes the translation of its target transcripts. DND1-interacting proteins
will be unbiasedly identified and using a variety of high-end microscopy tools, the localization of DND1, its target
transcripts, and translational machinery will be determined. The insight provided by these aims will provide a
novel paradigm for how an RBP regulates the epigenetic reprogramming of MGCS to ensure the
development of SSCs. In addition to advancing scientific knowledge, this fellowship proposal also exhibits high
training potential. The training plan describes a two-year blueprint designed to strengthen technical, professional,
and conceptual skills, which will be imp...

## Key facts

- **NIH application ID:** 10894637
- **Project number:** 5F32HD113220-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Talia Lee Hatkevich
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $62,269
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894637

## Citation

> US National Institutes of Health, RePORTER application 10894637, Regulation of Male Germ Cell Development through DND1-Mediated Translation of Epigenetic Factors (5F32HD113220-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894637. Licensed CC0.

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