# Identifying developmental trajectories characterized in the neuroepithelial stem cell to radial glia transition using single-cell transcriptomics

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $40,855

## Abstract

Project Summary/Abstract
The human cerebral cortex consists of billions of cells that are primarily generated during developmental
stages. During neural development, the neuroepithelium gives rise to radial glia, which is the canonical neural
stem cell. Radial glia then asymmetrically divide into transit amplifying intermediate progenitors, which
differentiate into excitatory neurons. These steps of neurogenesis have been well characterized in the
literature. However, there have been very few studies dedicated to understanding the molecular identity of
neuroepithelial stem cells, exploring the transition from neuroepithelial stem cell to radial glia, and teasing apart
their contribution to the neocortex. Here I leverage single-cell RNA sequencing data from primary cortical
samples through the BRAIN Initiative to reveal evidence of heterogeneity of neural stem cells in the first
trimester. Several gene candidates have already been identified through my analyses that are enriched in
progenitors during early first trimester development. I have identified two genes, DLK1 and HES4, both of
which are interestingly non-canonical players in the Notch signaling pathway. DLK1 and HES4 are both
enriched immediately in different progenitor populations before the switch from neuroepithelial stem cell to
radial glia. Lineage trajectory analysis using RNA velocity demonstrates a clear putative trajectory from the
neuroepithelial stem cell clusters to radial glial clusters. When I enriched for genes that influence RNA velocity
the most, DLK1 and HES4 were among the top genes influencing the cell fate switch. Therefore, I hypothesize
that DLK1 and HES4 are markers for neuroepithelial stem cells, and are important during the transition from
neuroepithelial stem cell to radial glia. To test my hypothesis, I will be performing genetic modulations of DLK1
and HES4 in cerebral organoids to determine if these genes are necessary and/or sufficient in neuroepithelial
stem cell production.

## Key facts

- **NIH application ID:** 9993052
- **Project number:** 1F31NS117121-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Ugomma Eze
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,855
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993052

## Citation

> US National Institutes of Health, RePORTER application 9993052, Identifying developmental trajectories characterized in the neuroepithelial stem cell to radial glia transition using single-cell transcriptomics (1F31NS117121-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993052. Licensed CC0.

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