The role of SASP in ischemic stroke: a deep dive into cellular mechanisms
BackgroundThe 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 wi...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1513357/full |
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| author | Dong Xie Yang Liu Fang-Biao Xu Jin-Sheng Zhang |
| author_facet | Dong Xie Yang Liu Fang-Biao Xu Jin-Sheng Zhang |
| author_sort | Dong Xie |
| collection | DOAJ |
| description | BackgroundThe 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.MethodsAggregated 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 real-time fluorescent polymerase chain reaction (RT-qPCR).ResultsFourteen 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.ConclusionThe 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. |
| format | Article |
| id | doaj-art-10dc75faa2ff4a348d39f930deed802f |
| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-10dc75faa2ff4a348d39f930deed802f2025-01-27T15:03:57ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-01-011510.3389/fneur.2024.15133571513357The role of SASP in ischemic stroke: a deep dive into cellular mechanismsDong Xie0Yang Liu1Fang-Biao Xu2Jin-Sheng Zhang3The Third Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Third Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, ChinaThe Third Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Encephalopathy, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaBackgroundThe 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.MethodsAggregated 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 real-time fluorescent polymerase chain reaction (RT-qPCR).ResultsFourteen 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fneur.2024.1513357/fullischemic strokeSASPsingle cell sequencing analysisimmune microenvironmentbasophilscell communication |
| spellingShingle | Dong Xie Yang Liu Fang-Biao Xu Jin-Sheng Zhang The role of SASP in ischemic stroke: a deep dive into cellular mechanisms Frontiers in Neurology ischemic stroke SASP single cell sequencing analysis immune microenvironment basophils cell communication |
| title | The role of SASP in ischemic stroke: a deep dive into cellular mechanisms |
| title_full | The role of SASP in ischemic stroke: a deep dive into cellular mechanisms |
| title_fullStr | The role of SASP in ischemic stroke: a deep dive into cellular mechanisms |
| title_full_unstemmed | The role of SASP in ischemic stroke: a deep dive into cellular mechanisms |
| title_short | The role of SASP in ischemic stroke: a deep dive into cellular mechanisms |
| title_sort | role of sasp in ischemic stroke a deep dive into cellular mechanisms |
| topic | ischemic stroke SASP single cell sequencing analysis immune microenvironment basophils cell communication |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1513357/full |
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