# Investigating Functional Ependymal Cell Heterogeneity in the Ventricular System

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $54,000

## Abstract

Project Summary/Abstract:
The brain is made up of highly specialized neurons and glia, organized spatially into distinct functional units,
interconnected to perform some of the most complex computations in nature. To date, cutting-edge molecular
and genetic tools have been applied overwhelmingly to the study of neural structure and function. Less well
understood are glial cells, despite the fact that radial glia generate all neurons in the central nervous system
during embryonic development. Adult neural stem cells (aNSCs) share many features of radial glia and
astrocytes, and in mice give rise to new neurons throughout life. aNSCs are present in the lateral walls of the
lateral ventricles, and sit in complex cellular niches that regulate many features of their activity. We and others
have previously found that the neurogenic potential of aNSCs depends on the aNSC’s position along the two-
dimensional surface of the ventricular wall. Dorsal aNSCs generate superficial-layer granular cells for the
olfactory bulb, while ventral aNSCs produce deep-layer granular cells. Adult NSC neurogenic potential is cell-
intrinsic, as heterotopically transplanted cells produce neurons consistent with their original position. However,
instructive niche cell signaling may also be regionally defined, as recent work demonstrates spatially selective
aNSC activation directly or indirectly by projection neurons in response to feeding behavior. Given the
widespread interest in stem cell therapies for brain repair, a critical gap in knowledge is the lack of mechanistic
insight into molecular determinants of aNSC neurogenic potential and of neurogenic niche regionalization. I
hypothesize that regionally-restricted transcriptional signatures define aNSC neurogenic potential, and
complementary signatures in niche glia underlie region-specific extrinsic control of adult neurogenesis. In this
proposal, I put forward three orthogonal Aims that span the K99 and R00 phases of the award. In the first two
Aims completed largely in the K99 phase, I use single cell sequencing to identify dorsal and ventral clusters of
aNSCs and niche glia, and mouse genetics to assess signature-driving gene contributions to regional identity.
The R00 phase is mainly accomplished in Aim 3, where I build on my existing preliminary single cell RNA-
sequencing analyses to gain mechanistic insight into functional heterogeneity among ependymal cells
throughout the ventricular system. Together, these data will provide a foundational understanding of
neurogenic niche signaling dynamics that together drive neurogenesis, and creates a new avenue of
exploration to understand the diverse roles of ependymal cells at the brain/cerebral spinal fluid interface.

## Key facts

- **NIH application ID:** 10456529
- **Project number:** 3K99NS121273-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Stephanie Redmond
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456529

## Citation

> US National Institutes of Health, RePORTER application 10456529, Investigating Functional Ependymal Cell Heterogeneity in the Ventricular System (3K99NS121273-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10456529. Licensed CC0.

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