# The role of Notch in establishing ovarian interstitial cells

> **NIH NIH FI2** · U.S. NATIONAL INST OF ENVIRON HLTH SCIS · 2021 · —

## Abstract

Project Summary
 Ovarian dysfunction is one of the leading causes behind women experiencing infertility in the United
States. Ovarian diseases and dysfunctions such as polycystic ovarian syndrome, androgen-producing tumors,
primary ovarian insufficiency, or hyperandrogenism contribute to infertility in women. Often these diseases result
from defects in ovary formation, particularly during fetal life. Formation of the fetal ovary requires the presence
of three main cell lineages: the germ cell lineage forms oocytes, the supporting cell lineage becomes granulosa
cells, and the interstitial cell lineage contribute to steroidogenic and non-steroidogenic stromal cell populations.
Germ cell and supporting cell lineages in the ovary are studied extensively due to the fact that these two cell
types form the follicles, the functional unit in the ovary. On the contrary, the interstitial cell lineage is less studied
despite that its dysfunction is associated with ovarian diseases. A critical knowledge gap on ovarian interstitial
cells is the cellular dynamics necessary for its specification and formation. The main goal of this application is to
fill this knowledge gap and lay the foundation for advances in disease diagnosis, treatment, and prevention by
using the mouse as the model.
 Within the applicant’s first year as a post-doctoral fellow in the Yao Laboratory, they discovered a unique
population of cells in the ovary that activate Notch and specifically develop into interstitial cells in adulthood
indicating that Notch may play a role in ovarian cell development. These findings lead to the central
hypothesis of this proposal: Notch activation establishes the interstitial cell lineage in the fetal ovary.
AIM 1 will investigate whether ovarian interstitial cell development requires Notch activation. This will be
accomplished by using a conditional and inducible genetic mouse model that silences Notch activation in the
progenitor interstitial cell population. AIM 2 will test whether ectopic Notch activation will transform the supporting
cells into interstitial cells through the use of separate, conditional, and inducible genetic mouse model that
specifically targets the supporting cell population. Ovaries from all of the genetic mouse models will be dissected,
morphologically analyzed, and subjected to single cell RNA sequencing for analysis. AIM 3 will investigate how
supporting cell and interstitial cell populations interact via the Notch pathway to define their unique identity. This
will be accomplished by performing single cell sequencing on lineage traced ovaries. This proposal will address
the involvement of the Notch activation in interstitial cell fate determination. Knowledge gained from this proposal
will provide a better understanding of how embryonic cells gain their progenitor identity and the mechanisms
driving ovarian interstitial cell development. With this information, future studies can directly address the impacts
of the environment or ...

## Key facts

- **NIH application ID:** 10273760
- **Project number:** 1FI2GM142559-01
- **Recipient organization:** U.S. NATIONAL INST OF ENVIRON HLTH SCIS
- **Principal Investigator:** Saniya Rattan
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273760

## Citation

> US National Institutes of Health, RePORTER application 10273760, The role of Notch in establishing ovarian interstitial cells (1FI2GM142559-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10273760. Licensed CC0.

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