# Transcriptional Control of adult hippocampal neural stem cell homeostasis

> **NIH NIH R56** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $507,776

## Abstract

Maintenance of somatic tissue functions necessitates stem cells to adaptively respond to
physiological signals and differentiate while ensuring self-preservation through regulation of
quiescence and self-renewal. Radial glia-like neural stem cells in the dentate gyrus subregion of
the adult hippocampus give rise to dentate granule cells and astrocytes, a process referred to as
adult hippocampal neurogenesis. Neural stem cells must balance long-term maintenance with
demands for differentiation and expansion in response to distinct physiological signals. These
fundamental decisions are governed by niche-signals that recruit cell-autonomous factors within
adult hippocampal neural stem cells. Although a growing number of studies have begun to
identify transcription factors that couple the regulation of adult hippocampal neural stem cell
quiescence with asymmetric self-renewal, the identities of transcription factors that couple
regulation of quiescence and symmetric self-renewal in the adult hippocampus (or adult brain)
are largely not known. Here, we will test the central hypothesis that Kruppel-like factor 9 (Klf9),
a zinc finger transcription factor, contributes to long-term maintenance and neural stem cell
expansion in the adult hippocampus through regulation of quiescence and symmetric stem cell
divisions. Towards this goal, we will build on our extensive preliminary data employing newly
engineered conditional Klf9 knock out and mCherry knock-in fusion mice, population and clonal
lineage tracing, and longitudinal live 2 photon imaging of individual adult hippocampal neural
stem cells in vivo. Execution of the proposed Aims will establish a foundation for understanding
how Klf9 levels in neural stem cells balance long-term preservation through regulation of
quiescence with rapid mobilization and expansion through control of symmetric self-renewal in
the adult brain. Insights gleaned from this proposal may guide strategies to replenish/expand the
pool of neural stem cells and restore hippocampal circuit plasticity in different disease states,
aging and following injury.

## Key facts

- **NIH application ID:** 10201930
- **Project number:** 1R56NS117529-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Amar Sahay
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $507,776
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201930

## Citation

> US National Institutes of Health, RePORTER application 10201930, Transcriptional Control of adult hippocampal neural stem cell homeostasis (1R56NS117529-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10201930. Licensed CC0.

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