# Investigating Functional Ependymal Cell Heterogeneity in the Ventricular System

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $125,010

## Abstract

Project Summary/Abstract:
Glial cells collectively outnumber neurons in the vertebrate brain, but mechanistic understanding of their
molecular subtypes and functions is lacking. Ependymal cells, ciliated epithelial cells that line the brain
ventricles and produce laminar flow of cerebral spinal fluid (CSF) with their many motile cilia, are one such
enigmatic group of glia. Relatively little is known about them, even compared to other glial cell types. Studies in
mice have demonstrated that ependymal cells are essential for normal brain function: the Alvarez-Buylla lab
and others have shown that defects in ependymal planar cell polarity or ciliary beating disrupt CSF flow. These
animals develop hydrocephalus, causing widespread damage throughout the brain due to increased
intracranial pressure. The view of ependymal cells as CSF conduits, however, has proven to be overly
simplistic. It is known that the largest neurogenic niche in the postnatal rodent brain, the ventricular-
subventricular zone (V-SVZ) is embedded in the lateral walls of the lateral ventricles. Ependymal cells form a
pinwheel-like structure around the CSF-contacting adult neural stem cells (aNSCs). Previous work from our lab
has shown that ependymal cells regulate aNSC neurogenesis via Noggin signaling. More recently, the lab has
described a morphologically distinct ependymal cell present in all brain ventricles that has only two motile cilia
and structurally atypical ciliary basal bodies. Strikingly, in the fourth ventricle the bi-ciliated cells extend a long
basal process from the ventricular surface into the Dorsal Raphe Nucleus (DRN), the primary source of
serotonin in the brain. Ependymal cells embedded in the V-SVZ regulate its neurogenic activity. However, a
critical gap in knowledge is our understanding of ependymal cell capacity to regulate the function of other
periventricular brain areas they directly contact, such as the DRN. A critical barrier to progress in
understanding ependymal cell heterogeneity is the lack of molecular markers and tools to independently
manipulate subpopulations of ependymal cells. To overcome these barriers, I have generated a single-cell
sequencing dataset from the V-SVZ and have analyzed ependymal cells and DRN neurons from a publicly
available single-cell sequencing dataset. Based on preliminary data, I hypothesize that ependymal cells are a
transcriptionally heterogeneous population, that have distinct functional roles in the V-SVZ and fourth ventricle.
In this proposal, I put forward two orthogonal Aims that span the K99 and R00 phases of the award. In the first
Aim I use single cell sequencing to identify heterogeneity among ependymal cells and adult neural stem cells
in the V-SVZ. The R00 phase is mainly accomplished in Aim 2, where I build on my existing preliminary single
cell RNA-sequencing analyses to gain mechanistic insight into functional heterogeneity among ependymal
cells in the fourth ventricle. Together, these data will provid...

## Key facts

- **NIH application ID:** 10374166
- **Project number:** 5K99NS121273-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Stephanie Redmond
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $125,010
- **Award type:** 5
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374166

## Citation

> US National Institutes of Health, RePORTER application 10374166, Investigating Functional Ependymal Cell Heterogeneity in the Ventricular System (5K99NS121273-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10374166. Licensed CC0.

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