# Generating spatial and functional maps of cell-to-cell interactions in MS lesions

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $558,575

## Abstract

Generating spatial and functional maps of cell-to-cell interactions in MS lesions
Single nucleus RNA sequencing (sNuc-Seq) studies have greatly advanced our understanding of
cellular heterogeneity in multiple sclerosis (MS) lesions. However, current CNS sNuc-Seq
protocols selectively under-sample astrocyte and microglia nuclei, resulting in low resolution of
population heterogeneity. Moreover, sNuc-Seq does not capture spatial information, such as
distribution and interactions of cell populations within the MS lesion environment.
Here, we propose to use a novel approach to sNuc-Seq of MS lesion tissue, enrichment for
unrepresented/rare nuclei such as astrocytes, microglia and infiltrating immune cells through Flow
sorting. We will combine this approach with advanced computational tools for denoising,
imputation and batch correction to improve recovery of biological signal and resolution of cellular
heterogeneity in acutely demyelinating, chronic active and remyelinating MS lesions. We will
leverage the subpopulation-specific transcriptomes to computationally predict possible
interactions between cell populations, based on expression of receptor-ligand pairs. We will
further use a highly multiplexed histology imaging approach to localize cellular subpopulations
and confirm co-localization of receptor-ligand pairs in MS lesions. We will finally conduct in vitro
studies to elucidate the functional impact of selected receptor-ligand interactions.
Our study will identify the constituent subpopulations and receptor-ligand interactomes that are
associated with acute demyelination, chronic low-grade inflammation and remyelination. These
interactions or combinations of interactions can be targeted to reduce inflammation or to enhance
neurorepair in MS. Moreover, our datasets will provide a rich resource that will guide more
functional studies on disease mechanisms.

## Key facts

- **NIH application ID:** 10136972
- **Project number:** 1R01NS118886-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** David Pitt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $558,575
- **Award type:** 1
- **Project period:** 2021-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136972

## Citation

> US National Institutes of Health, RePORTER application 10136972, Generating spatial and functional maps of cell-to-cell interactions in MS lesions (1R01NS118886-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10136972. Licensed CC0.

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