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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1513357
This article is part of the Research Topic Spatial Transcriptome and Single-Cell Sequencing for Exploring Molecular Mechanisms of Neuroimmunity and Discovering Novel Markers of Neurological Diseases View all 5 articles

The Role of SASP in Ischemic Stroke: A Deep Dive into Cellular Mechanisms

Provisionally accepted
Dong Xie Dong Xie 1Yang Liu Yang Liu 1Fang-biao Xu Fang-biao Xu 2Jin-Sheng Zhang Jin-Sheng Zhang 3*
  • 1 Henan University of Chinese Medicine, Zhengzhou, China
  • 2 Center of Encephalopathy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, China
  • 3 Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, China

The final, formatted version of the article will be published soon.

    The escalating incidence of ischemic stroke (IS) exerts a heavy toll on global health. Aging, a prominent risk factor, implicates the senescence-associated secretory phenotype (SASP) in IS pathogenesis. We postulated that alterations in SASP-related factor expression during IS correlate with remodeling of intercellular interaction networks and disease advancement. The present study endeavored to preliminarily dissect the SASP-IS nexus via combined bulk and single-cell transcriptome analysis. Methods: Aggregated expression profiles from human peripheral blood bulk chips and MCAO mouse single-cell sequencing data, followed by SASP gene analysis. Executed protein interaction network and enrichment assays. Investigated immune infiltration in stroke patients, managed quality control and annotation of single-cell data, cherry-picked central cells based on SASP scores, unearthed essential genes via enrichment analysis, conducted pseudo-time and intercellular communication studies, and prognosticated drugs for hub genes. Finally, authenticated core gene expression in serum of MCAO and Sham rats using RT-qPCR. Results: Fourteen hub genes were discerned. Seven cell types were annotated in MCAO mouse peripheral blood single-cell data. Basophils exhibited the highest SASP scores, with Lcp1 upregulated and Ccl3 downregulated in basophils of the MCAO group. Enrichment analysis divulged a significant association of Ccl3 with the cell apoptosis pathway and Lcp1 with immune responses. The Ccl3 gene is pivotal in basophils and basophil-neutrophil crosstalk. Additionally, we forecasted nagrestipen's regulatory function on Ccl3. RT-qPCR demonstrated a marked elevation in Lcp1 mRNA and a pronounced reduction in Ccl3 in the MCAO group relative to the Sham group.The Ccl3 gene in basophils and its immune cell interaction is a linchpin in the IS immune microenvironment. Ccl3 and Lcp1 might potentially modulate IS progression by influencing SASP, proffering novel prospects for IS clinical diagnosis and treatment.Ischemic Stroke (IS) exhibits a serious health concern, as emphasized by a 2022 report from the American Heart Association, stating that roughly 795,000 people undergo strokes each year.

    Keywords: ischemic stroke, SASP, Single cell sequencing analysis, immune microenvironment, Basophils, Cell Communication

    Received: 18 Oct 2024; Accepted: 17 Dec 2024.

    Copyright: © 2024 Xie, Liu, Xu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jin-Sheng Zhang, Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450046, Henan Province, China

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