# Single cell transcriptomics to determine stroke etiology and outcomes after thrombectomy

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $460,625

## Abstract

Project Summary
Acute ischemic stroke (AIS) is a significant cause of morbidity and mortality in the United States
and worldwide. Undoubtedly, the emergence of mechanical thrombectomy (MT) as a standard
of care for anterior circulation large vessel occlusions (LVOs) has improved stroke outcomes.
Notwithstanding, the burden of disease remains significant. Even when patients with AIS-LVO
receive MT, only ~ 70% achieve successful revascularization and more than half of patients
remain with moderate-to-severe disability. The problem is exacerbated by the high proportion of
cryptogenic stroke in the AIS-LVO population for which effective and targeted secondary stroke
prevention strategies cannot be implemented. To date, little is known about how clot biology
informs stroke etiology, revascularization success, and stroke outcomes.
In our preliminary work, we have leveraged access to clot tissue retrieved at MT from the middle
cerebral artery (MCA) to determine whether modern cellular transcriptional profiling, i.e., single-
cell RNA sequencing (scRNA-seq), can provide insight into stroke etiology and mechanisms of
thromboembolism. We uncovered a surprising enrichment and diversity of immune cells within
the clot including granulocytes, macrophages, T cells and natural killer (NK) cells. These cellular
constituents and their transcriptional signatures differed by stroke etiology. We also found low-
abundance cardiac endothelial cells in the embolized clot of a patient with cryptogenic stroke, a
powerful indicator of the embolic source. Finally, our data suggested a role for neutrophil
extracellular traps (NETs) in clot biology, an emerging determinant of recanalization success.
Given these findings, we hypothesize that the cellular and transcriptional profiles revealed by
scRNA-seq of clots retrieved at MT will point to stroke etiology, correlate with revascularization
success and patient outcomes, and uncover basic mechanisms of thromboembolism relevant to
stroke pathophysiology. These hypotheses will be addressed in the experiments of the following
Specific Aims: (1) to determine whether the complexity of cellular diversity in clot retrieved at
MT and their molecular alterations differentiate between stroke etiologies; and (2) to determine
whether transcriptional profiles of clots retrieved at MT inform revascularization success and
patient outcomes.
The insights gleaned from the proposed studies have the potential to be rapidly translated to the
bedside, especially as it relates to an accurate determination of stroke etiology and biological
basis for revascularization success.

## Key facts

- **NIH application ID:** 10110594
- **Project number:** 1R21NS119992-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Charles Matouk
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $460,625
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110594

## Citation

> US National Institutes of Health, RePORTER application 10110594, Single cell transcriptomics to determine stroke etiology and outcomes after thrombectomy (1R21NS119992-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10110594. Licensed CC0.

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