# Identification of candidate juvenile protective factors in neuron, glia, and vascular cells of human and mouse brain

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $150,400

## Abstract

Project Summary/Abstract
Glia (astrocytes, microglia, and oligodendrocytes) and vascular cells are critical for the development
and function of the central nervous system. Glial and vascular defects are associated with aging
and neurodegeneration. Juvenile brains exhibit remarkable plasticity and resilience that diminish when
brains mature. The potential contribution of glia and vascular cells to the plasticity of juvenile brains
and the diminution of regenerative potentials in adult and aging brains remain poorly understood.
Investigating molecular differences between juvenile and mature glia and vascular cells holds promise for
the identification of protective factors in the brain. We recently developed immunopanning methods to
purify astrocytes, microglia, oligodendrocytes, neurons, and vascular cells from both human and mouse
brains. Cell populations isolated by immunopanning have high purity and produce abundant RNA for
transcriptome profiling by RNA-sequencing (RNA-seq). Sequencing of purified populations of cells provides
higher sensitivity for the detection of differential gene expression than alternative methods such as single
cell RNA-seq. Using immunopanning, we purified astrocytes from a series of developmental stages from
both human and mouse brains. In this proposed study, we will first perform bioinformatics analysis of our
juvenile and mature astrocyte datasets and identify differentially expressed genes at each stage (Aim 1).
Human and mouse evolution separated about 100 million years ago. Translating discoveries made in
mouse models into clinics has been challenging. Our human and mouse astrocyte datasets will allow us to
identify developmentally regulated molecular pathways preserved through a hundred million years of
evolution and therefore likely to be essential. These analyses will generate candidate astrocytic juvenile
protective factors that can be tested in future studies. Furthermore, we will expand our RNA-seq comparison
of juvenile and mature cells to neurons, microglia, oligodendrocytes, and endothelial cells using
immunopanning purified cell populations (Aim 2). These systematic analyses have the potential to reveal
candidate juvenile protective factors in each cell type, improve our understanding of the roles played by
each cell type in brain maturation and aging, and uncover candidate molecular pathways to target in the
treatment of aging and neurodegeneration. The proposed study will build the foundation for a larger scale
study that tests the function of candidate juvenile protective factors in neurons, glia, and vascular cells.

## Key facts

- **NIH application ID:** 9877889
- **Project number:** 1R03AG065772-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Ye Zhang
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,400
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877889

## Citation

> US National Institutes of Health, RePORTER application 9877889, Identification of candidate juvenile protective factors in neuron, glia, and vascular cells of human and mouse brain (1R03AG065772-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9877889. Licensed CC0.

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