Academic Journal
The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species
العنوان: | The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species |
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المؤلفون: | Kevin C. Bermea, Nicolas Kostelecky, Sylvie T. Rousseau, Chieh-Yu Lin, Luigi Adamo |
المصدر: | Frontiers in Immunology, Vol 13 (2022) |
بيانات النشر: | Frontiers Media S.A. |
سنة النشر: | 2022 |
المجموعة: | Directory of Open Access Journals: DOAJ Articles |
مصطلحات موضوعية: | B-cells, heart, cardiology, cardiac immunology, cardiac inflammation, naive B-cells, Immunologic diseases. Allergy, RC581-607 |
الوصف: | IntroductionCardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.MethodsWe performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells (PBMCs). We validated these findings on primary B-cells sorted from the heart and peripheral blood of left ventricular assistive device recipients. To identify biological pathways upregulated in myocardial B-cells across species, we compared differential gene expression in myocardial vs peripheral blood B-cells across the studied human datasets and published rodent datasets.ResultsIn healthy human heart samples, we found B-cells at a ratio of 1:8 compared to T-cells (2.41 ± 0.45 vs 19.36 ± 4.43, p-value <0.001). Myocardial B-cells were more abundant in the interstitium compared with the intravascular space (p-value=0.011), and also more abundant in the myocardium vs. epicardium (p-value=0.048). Single-cell gene expression analysis showed that the human myocardium harbored mostly naive B-cells with a gene expression profile distinct from that of PBMC B-cells. Cross-comparison of differentially-expressed genes in myocardial vs. PBMC B-cells across human and rodent datasets identified 703 genes with consistent differential gene expression across species (binomial p-value=2.9e-48). KEGG pathway analysis highlighted “B-cell receptor signaling pathway,” “Antigen processing and presentation,” and “Cytokine-cytokine receptor interaction” among the top pathways upregulated in cardiac B-cells (FDR <0.001) ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 1664-3224 |
Relation: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.973211/full; https://doaj.org/toc/1664-3224; https://doaj.org/article/2b1a252758f247c3ba38a152532ff328 |
DOI: | 10.3389/fimmu.2022.973211 |
الاتاحة: | https://doi.org/10.3389/fimmu.2022.973211 https://doaj.org/article/2b1a252758f247c3ba38a152532ff328 |
رقم الانضمام: | edsbas.D20AAB1 |
قاعدة البيانات: | BASE |
تدمد: | 16643224 |
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DOI: | 10.3389/fimmu.2022.973211 |