# A multi-modal, brain-wide atlas of astrocyte diversity across developmental stages and model species

> **NIH NIH F31** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $48,994

## Abstract

PROJECT SUMMARY
Astrocytes influence neuronal circuit assembly and function and have been shown to respond, modulate, and
drive disease pathogenesis. Despite this, relatively little is known about astrocyte diversity across brain regions,
development, and species. However, recent single-cell RNA sequencing studies demonstrate that astrocytes
have significant transcriptomic heterogeneity across the brain. Detailed molecular and cellular characterization
of these subpopulations is needed to determine whether molecularly-defined astrocyte subpopulations serve
distinct functions in both health and disease. Thus, the goal of this project is to use cutting-edge techniques to
characterize the transcriptomic, structural, and functional diversity of astrocyte subpopulations across
developmental stages and disease-relevant brain regions in the mouse and marmoset brain. By conducting a
detailed analysis of over 70,000 astrocyte nuclei across eight brain regions in the young adult marmoset, I have
discovered striking regional heterogeneity among astrocytes, particularly between cortical and subcortical
regions. In this proposal, I aim to make three significant advances: a) map the evolution of astrocyte regional
heterogeneity across development, b) compare this heterogeneity between rodent and non-human primate
species, and c) characterize the functional identities of transcriptomically distinct astrocyte subtypes. To address
the first two of these, I will conduct single-nucleus RNA sequencing of four brain regions in the embryo, neonate,
juvenile, and adolescent marmoset and mouse. To address the third, I will use expansion microscopy to assess
whether molecularly-defined astrocyte subtypes have distinct morphologies, ensheathment of synapses, and/or
configuration of ion channels at the nanoscale. Additionally, I will image astrocyte calcium dynamics, considered
key components of signaling processes used by astrocytes to regulate neuronal networks, in acute brain slices
from both mouse and marmoset to characterize the functional diversity of transcriptomically-defined astrocyte
subtypes. The proposed study will mark the first cross-species, cross-development, cross-region molecular
profile of brain cells using consistent experimental and computational methodology, and will create new
knowledge about the development of astrocyte heterogeneity across brain regions in rodents and non-human
primates. Importantly, this detailed molecular and cellular characterization of astrocyte subpopulations will
facilitate their precise manipulation for basic and translational research on neurodevelopmental and psychiatric
disorders. I will carry out this project in the labs of Dr. Guoping Feng and Dr. Ed Boyden in the Brain and Cognitive
Sciences Department at the Massachusetts Institute of Technology. The Feng and Boyden labs contain all
required equipment for the proposed project. All necessary training regarding required laboratory and
computational techniques will be pr...

## Key facts

- **NIH application ID:** 10825433
- **Project number:** 5F31MH133329-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Margaret Elizabeth Schroeder
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,994
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825433

## Citation

> US National Institutes of Health, RePORTER application 10825433, A multi-modal, brain-wide atlas of astrocyte diversity across developmental stages and model species (5F31MH133329-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10825433. Licensed CC0.

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