# Extreme cell growth in support of stem cell proliferation and niche exit

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $382,214

## Abstract

K. Gordon, UNC R35 Abstract
The specification and robust maintenance of the germ line stem cells and their differentiated descendants that
form gametes are essential to the success of an organismal lineage. Stem cell niches are primary regulators of
stem cell fate, which is characterized by continuous self-renewal with the capability of differentiation. Therefore
the structure of stem cell niches—which often have extensive cellular contacts with their supported stem cell
populations that must be broken by daughter cells that go on to differentiate—appear crucial for the regulation
of the cell fate decision. Such contacts are shared in a variety of stem cell niches, but studies relating niche
structure to function lag behind genetic analysis of stem cell regulation. Stem cell niches lie deep in tissues,
making them difficult to observe, and stem cell divisions are stochastic. This proposal avoids these challenges
by studying the germ line stem cell niche of C. elegans, an animal that is suited to multiplex in vivo imaging.
The overall goal for the research program is to discover how undifferentiated germ stem cells receive cues
from their micro-environment to stimulate proliferation and the cell fate switch to gamete differentiation, and
how the dynamic cell structures supporting germ stem cells form. Conserved proliferation and cell growth
pathways are relevant to human health. Pursuit of these questions will lead to insights that, like other findings
made in this canonical stem cell niche model, may be broadly applicable to other stem cell systems.
Overview of research and goals for the next five years: The Gordon Lab opened at UNC just before the
pandemic began. It pursues key questions like: How do the stem cell niche and gonad sheath cells grow and
internally partition themselves to interact appropriately with germ cells at different steps of the differentiation
program? Both the niche cell and sheath undergo substantial growth and transformation during development.
Both somatic cells will be genetically manipulated to determine if effects on germ cell proliferation are mediated
by growth and partitioning of these regulatory cells. Cell-specific RNAi strains will be used to screen for genes
resulting in diminished Sh1 growth and germ cell proliferation. What molecular mechanisms underlie oriented
cell divisions at the niche boundary and asymmetrical cell fate acquisition? Spindle orientation has been
studied in great detail in early C. elegans embryos, but it was not known that divisions in proliferating germ
cells were oriented. Adhesion between the niche and germ cells was a neglected area of inquiry until recent
findings implicated cadherin complexes—which orient spindles in the embryo—in the dramatic wrapping
behavior of the niche around the stem cells. How does the stem cell niche mature from larvae to adults? RNA-
seq of niche cells across the larva/adult transition will identify candidate genes that are correlated with the
transition f...

## Key facts

- **NIH application ID:** 10501818
- **Project number:** 1R35GM147704-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kacy Lynn Gordon
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,214
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501818

## Citation

> US National Institutes of Health, RePORTER application 10501818, Extreme cell growth in support of stem cell proliferation and niche exit (1R35GM147704-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10501818. Licensed CC0.

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