# Cellular and Molecular Mechanisms of Germline Regeneration

> **NIH NIH R35** · MARINE BIOLOGICAL LABORATORY · 2021 · $166,868

## Abstract

PROJECT SUMMARY
Humans and well-established research organisms lack the ability to regenerate their reproductive cells (germ
cells) and reproductive organs. Research findings from these organisms established the current view that germ
cells are a distinct lineage separated from the soma; therefore, the loss of germ cells renders an organism infertile
because new germ cells cannot be derived from the soma. Contradicting this widely accepted view is the fact
that many organisms (e.g. hydra, flatworms, segmented worms, and sea stars) can readily regenerate germ
cells. However, the cellular source of regenerated germ cells in these organisms is very poorly understood. The
goal of my laboratory is to close this knowledge gap and define the cellular origins and molecular
mechanisms of germ cell regeneration. Addressing this is not feasible using established research organisms
like mice, fruit flies, and nematodes, because they do not regenerate germ cells. Furthermore, many of the
organisms that can regenerate germ cells are not conducive to studying the mechanisms of this process because
they lack transgenic tools, or their anatomies present technical challenges such as large and opaque bodies, or
inaccessibility of reproductive organs. These limitations prevent the use of live imaging – a key tool to trace the
lineages of germ cells and their source cells. We use a segmented worm, Platynereis dumerilii, for studying germ
cell regeneration. Platynereis is well-suited for this study because germ cell regeneration can be induced and is
achieved quickly; transcriptome databases, a draft genome, and transgenic tools (critical for genetic lineage
tracing) are available; and a small and transparent body makes it excellent for live imaging. Therefore,
Platynereis is a research organism that presents a rare opportunity to combine the modern techniques
required to study germ cell regeneration (live-imaging, genetic lineage tracing, transcriptomics) in the
relevant post-embryonic life stages (i.e. juveniles, adults) which are typically challenging to image live.
We postulate three possible models for the cellular sources for the regenerated germ cells: 1) pluri/multipotent
stem cells regenerate both somatic and germ cells; 2) a lineage-restricted cell population is dedicated to
regenerating only the germ cells; or 3) somatic cells transdifferentiate into germ cells by reprogramming. Our
experimental approach will be to: a) Test between the three cellular models of germ cell regeneration via genetic
cell lineage tracing and live imaging. This will allow us to identify the exact cell lineages that give rise to germ
cells during development and regeneration. b) Identify the molecular changes taking place during reprogramming
source cells into germ cells by single cell RNA sequencing. This will allow us to obtain transcriptome trajectories
over the course of regeneration and identify cell type-specific markers in the source cells, the intermediate states,
and the n...

## Key facts

- **NIH application ID:** 10197976
- **Project number:** 5R35GM138008-02
- **Recipient organization:** MARINE BIOLOGICAL LABORATORY
- **Principal Investigator:** Busra Duygu Ozpolat
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $166,868
- **Award type:** 5
- **Project period:** 2020-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197976

## Citation

> US National Institutes of Health, RePORTER application 10197976, Cellular and Molecular Mechanisms of Germline Regeneration (5R35GM138008-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197976. Licensed CC0.

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