# Mechanisms of quiescence in primordial germ cells

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $330,664

## Abstract

Project Summary
 Quiescence is a common character of many stem cells. Low metabolic activity in these cells may
function to minimize the potential damaging effects of stress, minimize the number of cells needed for
replenishment, and may occupy unique niches. These cells are found in many adult human tissues, even in the
tissues of the central nervous system. These naturally occurring stem cells however, are rare and difficult to
isolate so a mechanistic understanding of their integrated cellular activities is largely unknown.
 We recently learned that the primordial germ cells (PGC) of the sea urchin are quiescent. From a highly
active early embryonic cell, they rapidly and dramatically change their metabolic pathways, decrease their
protein synthesis, have low mRNA turnover and diminished transcription, and reduced mitochondrial activity.
These cells are quiescent at a time when the remainder of the embryo multiplies to thousands of cells with
many unique gene and protein expression patterns. Following the quiescent period, the PGCs rapidly return to
normal cellular activity. Thus, the phenotype is prolonged, inclusive, highly penetrant, and transient. Resolution
of the phenotype will require large numbers of naturally occurring, isolated PGCs, high throughput molecular
manipulations, quantitative biochemical approaches, and excellent clarity for in vivo optics – features ideally
suited for sea urchin embryos. This application will interrogate the molecular mechanism of this transient
quiescence and the dramatic phenotypic changes in the stem cells of the germ line. Stem cell quiescence is
shared by many stem cell types, in and out of the germ line, but sparingly few models are present to explore
such mechanisms in abundance, in naturally occurring cells, and in vivo.
 Overall the novelty and impact of this work includes: 1) germline stem cells using oxidative glycolysis
but without proliferation – distinct from the Warburg effect; 2) broad, quantitative quiescence characters; 3)
integration of metabolism with molecular mechanisms for quiescence; 4) analysis of quiescence on
developmental potential of the stem cell, and 5) the cells studied are primordial germ cells, a cell type found in
all sexually reproducing animals. Coupled with a tractable model system for study, this proposal provides
outstanding potential to add to an exciting field of both basic and clinical interest for generation of sperm and
eggs in the adult.

## Key facts

- **NIH application ID:** 9978591
- **Project number:** 5R01GM125071-26
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** GARY M WESSEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,664
- **Award type:** 5
- **Project period:** 1991-05-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978591

## Citation

> US National Institutes of Health, RePORTER application 9978591, Mechanisms of quiescence in primordial germ cells (5R01GM125071-26). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978591. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*