# Spatial transcriptional phenotyping of Sjögren’s disease tissue-resident mesenchymal stromal cells and neighbors in labial salivary glands

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2023 · $154,052

## Abstract

PROJECT SUMMARY
Sjögren’s disease (SjD), a systemic autoimmune disease that affects four million people in the United States and
impairs health-related quality of life, has no FDA-approved disease-modifying treatments available. Current trials
include only a narrow subset of SjD patients who are anti-SSA antibody positive (SSA+), excluding 25% of SjD
patients who are anti-SSA antibody negative (SSA-). SSA- SjD patients have distinct clinical phenotypes from
SSA+ patients. Recently, mesenchymal stromal cells (MSCs) have been implicated in SjD salivary gland
pathobiology and represent a novel targetable cell type in this disease. Thus, there is a critical need to develop
new targeted therapy that takes into account the heterogeneity of SSA+ and SSA- SjD patients and to further
define the role of MSCs in the pathogenesis of SjD. Our long-term goal is to use SjD pathogenic insights to
create new cell-targeted therapy. The goal of this project is to define the transcriptomics of MSCs within salivary
gland tissue. We also will determine the lymphocyte subsets in proximity to salivary gland MSCs and determine
how these subsets differ between control and SjD glands and, within SjD, between SSA+ and SSA- glands. We
hypothesize that SjD has unique MSC subtypes and they will promote differential local cellular milieu from
controls and between SSA+ and SSA- subjects. The rationale for this hypothesis is based on our data showing
IFN𝛾-treated MSCs are capable of acting as antigen-presenting cells and promoting T-cell chemotaxis. The
central hypothesis will be tested by pursuing two specific Aims. Aim 1 will provide an integral understanding of
the SjD transcriptional phenotype of a novel cell type, the MSC, compared to controls. Aim 2 will define how the
cellular molecular framework of MSCs and overall inflammatory cell composition differs between SSA+ and SSA-
subjects. To accomplish these Aims, FISH combined with Hybridization Chain Reaction based signal
amplification will be used to perform spatial genomics and rapid multiplexed immunofluorescence protein
profiling of salivary gland tissue. MSC subtypes, lymphocyte interactions with MSCs, and differential lymphocyte
composition between control, SSA+ and SSA- subjects will be determined using a series of spatially resolved
cell state and interaction analyses. This project builds an interdisciplinary team integrating experts from single
cell biotechnology, SjD and rheumatology, stem cell biology, pathology, and bioinformatics to create an atlas of
MSC phenotypes that can be used to enhance SjD’s stem cell therapies. The proposed application is innovative
because it uses cutting-edge technology to define spatial genomics and proteomics of salivary gland tissue and
shifts from the traditional focus on SSA+ subjects alone, toward differences between SSA+ and SSA- salivary
glands. This research is significant because it defines SjD MSCs, a potential novel therapeutic target, and
because it details spatial profil...

## Key facts

- **NIH application ID:** 10575107
- **Project number:** 1R21DE032475-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ahmet F. Coskun
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $154,052
- **Award type:** 1
- **Project period:** 2023-09-08 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10575107

## Citation

> US National Institutes of Health, RePORTER application 10575107, Spatial transcriptional phenotyping of Sjögren’s disease tissue-resident mesenchymal stromal cells and neighbors in labial salivary glands (1R21DE032475-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10575107. Licensed CC0.

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