# Characterization of Neural Stem Cells in Adult Brain

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $649,245

## Abstract

The identification of postnatal neural stem cells is essential to understand neural development, adult
neurogenesis and gliogenesis, and the origin of brain tumors. Neural stem cells (NSCs) have been identified
as a subpopulation of ventricle contacting astroglial (B1) cells in the ventricular-subventricular zone (V-SVZ) of
the adult rodent brain. Our recent work has shown that B1 cells give rise to a second population of V-SVZ
astroglial (B2) cells that do not contact the ventricle. The function of B2 cells is not known, but it has been
suggested that B2 cells could function as secondary NSCs in rodents. Whether similar NSCs exist in the V-SVZ of the postnatal human brain remains unknown. Our studies in humans have revealed an extensive
migration and recruitment of new neurons in the anterior forebrain of children younger than 6 months of age.
Interestingly, astroglial cells with B1-like (hB1) and B2-like characteristics are present in the walls of the lateral
ventricles in the human brain. hB1 cells are present at birth, but rapidly disappear within the first five months
after birth. During this period, a sub-ependymal ribbon of human B2-like (hB2) cells forms next to the lateral
ventricle walls. Preliminary data show that these hB2 cells are distinct from parenchymal astrocytes, continue
to proliferate postnatally and have marker expression similar to embryonic radial glial. Our hypothesis is that
hB2 cells lose apical attachment with the ventricle, but retain neural stem cell (NSC) properties to generate
new neurons in the infant human brain. We hypothesize that this transformation of hB1 to hB2 cells is similar
to the apical-basal transition that occurs in mice as B1 cells give rise to B2 cells, and that these secondary
mouse (relay) progenitors retain NSC functions. Our objective is to characterize mouse and human B2
cells, trace their origin and determine if they have NSC properties. We propose three specific aims: Aim
1: We will use single cell genomics and high-resolution light and electron microscopy to define
morphological and transcriptomic profiles of mouse and human B2 cells. Aim 2: We will use selective
labeling, cell purification and transplantation to determine the function of mouse B2 cells. Aim 3: We
will purify human V-SVZ astrocytes and test their progenitor potential in vitro and by
xenotransplantation into the adult mouse brain. This new knowledge will impact our understanding of
human brain development and postnatal neurogenesis, aiding in the discovery of developmental origins of
neurological disorders in children and adults. The precise identification of a new human cell type with
neurogenic potential could also be key for regenerative medicine and to trace the origin of brain tumors.

## Key facts

- **NIH application ID:** 9972606
- **Project number:** 2R01NS028478-27
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Arturo Alvarez-Buylla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $649,245
- **Award type:** 2
- **Project period:** 1990-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972606

## Citation

> US National Institutes of Health, RePORTER application 9972606, Characterization of Neural Stem Cells in Adult Brain (2R01NS028478-27). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9972606. Licensed CC0.

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