Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context
Background: Each heartbeat is initiated in the sinoatrial node (SAN), and although a recent study (GSE130710) using single nucleus RNA-seq had discovered different populations of cell types within SAN tissue, the distinct potential functions of these cell types have not been delineated. Methods: To...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022039962 |
| _version_ | 1811173448865546240 |
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| author | Jia-Hua Qu Richard Telljohann Rostislav Byshkov Edward G. Lakatta |
| author_facet | Jia-Hua Qu Richard Telljohann Rostislav Byshkov Edward G. Lakatta |
| author_sort | Jia-Hua Qu |
| collection | DOAJ |
| description | Background: Each heartbeat is initiated in the sinoatrial node (SAN), and although a recent study (GSE130710) using single nucleus RNA-seq had discovered different populations of cell types within SAN tissue, the distinct potential functions of these cell types have not been delineated. Methods: To infer some special potential functions of different SAN cell clusters, we applied principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP) to the GSE130710 dataset to reduce dimensions, followed by Pseudotime trajectory and AUCell analyses, ANOVA and Hurdle statistical models, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments to determine functional potential of cell types. Nuclear EdU immuno-labeling of SAN tissue confirmed cell type proliferation. Findings: We identified elements of a coupled clock system known to drive SAN cell pacemaking within the GSE130710 sinus node myocyte cluster, which, surprisingly, manifested signals of suppressed fatty acid and nitrogen metabolism and reduced immune gene expression. Proliferation signaling was enriched in endocardial, epicardial, epithelial cells, and macrophages, in which, fatty acid and nitrogen metabolic signals were also suppressed, but immune signaling was enhanced. EdU labeling was rare in pacemaker cells but was robust in interstitial cells. Interpretation: Pacemaker cells that initiate each heartbeat manifest suppressed fatty acid and nitrogen metabolism and limited immune signaling and proliferation potential. In contrast, other populations of SAN cells not directly involved in the initiation of heartbeats, manifest robust proliferation and immune potential, likely to ensure an environment required to sustain healthy SAN tissue pacemaker function. |
| first_indexed | 2024-04-10T17:47:05Z |
| format | Article |
| id | doaj.art-f8b73796d09746ed971850cff7203e36 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-10T17:47:05Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-f8b73796d09746ed971850cff7203e362023-02-03T04:58:41ZengElsevierHeliyon2405-84402023-01-0191e12708Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in contextJia-Hua Qu0Richard Telljohann1Rostislav Byshkov2Edward G. Lakatta3Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USALaboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USALaboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USACorresponding author.; Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USABackground: Each heartbeat is initiated in the sinoatrial node (SAN), and although a recent study (GSE130710) using single nucleus RNA-seq had discovered different populations of cell types within SAN tissue, the distinct potential functions of these cell types have not been delineated. Methods: To infer some special potential functions of different SAN cell clusters, we applied principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP) to the GSE130710 dataset to reduce dimensions, followed by Pseudotime trajectory and AUCell analyses, ANOVA and Hurdle statistical models, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments to determine functional potential of cell types. Nuclear EdU immuno-labeling of SAN tissue confirmed cell type proliferation. Findings: We identified elements of a coupled clock system known to drive SAN cell pacemaking within the GSE130710 sinus node myocyte cluster, which, surprisingly, manifested signals of suppressed fatty acid and nitrogen metabolism and reduced immune gene expression. Proliferation signaling was enriched in endocardial, epicardial, epithelial cells, and macrophages, in which, fatty acid and nitrogen metabolic signals were also suppressed, but immune signaling was enhanced. EdU labeling was rare in pacemaker cells but was robust in interstitial cells. Interpretation: Pacemaker cells that initiate each heartbeat manifest suppressed fatty acid and nitrogen metabolism and limited immune signaling and proliferation potential. In contrast, other populations of SAN cells not directly involved in the initiation of heartbeats, manifest robust proliferation and immune potential, likely to ensure an environment required to sustain healthy SAN tissue pacemaker function.http://www.sciencedirect.com/science/article/pii/S2405844022039962Sinoatrial nodeSingle nucleus RNA-seqPacemakerProliferationMetabolismImmune |
| spellingShingle | Jia-Hua Qu Richard Telljohann Rostislav Byshkov Edward G. Lakatta Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context Heliyon Sinoatrial node Single nucleus RNA-seq Pacemaker Proliferation Metabolism Immune |
| title | Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context |
| title_full | Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context |
| title_fullStr | Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context |
| title_full_unstemmed | Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context |
| title_short | Characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionResearch in context |
| title_sort | characterization of diverse populations of sinoatrial node cells and their proliferation potential at single nucleus resolutionresearch in context |
| topic | Sinoatrial node Single nucleus RNA-seq Pacemaker Proliferation Metabolism Immune |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022039962 |
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