Decoding aging in the heart via single cell dual omics of non-cardiomyocytes

Summary: To understand heart aging at the single-cell level, we employed single-cell dual omics (scRNA-seq and scATAC-seq) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardi...

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Main Authors: Yiran Song, Li Wang, Haofei Wang, Hong Ma, Jun Xu, Jiandong Liu, Li Qian
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224026968
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author Yiran Song
Li Wang
Haofei Wang
Hong Ma
Jun Xu
Jiandong Liu
Li Qian
author_facet Yiran Song
Li Wang
Haofei Wang
Hong Ma
Jun Xu
Jiandong Liu
Li Qian
author_sort Yiran Song
collection DOAJ
description Summary: To understand heart aging at the single-cell level, we employed single-cell dual omics (scRNA-seq and scATAC-seq) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardiomyocytes. Our analysis revealed aging response heterogeneity and its dynamics over time. Immune cells, notably macrophages and neutrophils, showed significant aging alterations, while endothelial cells displayed moderate changes. We identified distinct aging signatures within the cell type, including differential gene expression, transcription factor activity, and motif variation. Sub-cluster analysis revealed intra-cell type heterogeneity, characterized by diverse aging patterns. The senescence-associated secretory phenotype emerged as a key aging-related phenotype. Moreover, aging significantly influenced cell-cell communication, especially impacting a fibroblast sub-cluster with high expression of ERBB4. This study elucidates the complex cellular and molecular landscape of cardiac aging and offers guidance for potential therapeutic avenues to treat aging-related heart diseases.
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spelling doaj-art-610a4f740b984d45928b86ce2ad0c2712024-12-22T05:29:28ZengElsevieriScience2589-00422024-12-012712111469Decoding aging in the heart via single cell dual omics of non-cardiomyocytesYiran Song0Li Wang1Haofei Wang2Hong Ma3Jun Xu4Jiandong Liu5Li Qian6Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USADepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA; Corresponding authorSummary: To understand heart aging at the single-cell level, we employed single-cell dual omics (scRNA-seq and scATAC-seq) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardiomyocytes. Our analysis revealed aging response heterogeneity and its dynamics over time. Immune cells, notably macrophages and neutrophils, showed significant aging alterations, while endothelial cells displayed moderate changes. We identified distinct aging signatures within the cell type, including differential gene expression, transcription factor activity, and motif variation. Sub-cluster analysis revealed intra-cell type heterogeneity, characterized by diverse aging patterns. The senescence-associated secretory phenotype emerged as a key aging-related phenotype. Moreover, aging significantly influenced cell-cell communication, especially impacting a fibroblast sub-cluster with high expression of ERBB4. This study elucidates the complex cellular and molecular landscape of cardiac aging and offers guidance for potential therapeutic avenues to treat aging-related heart diseases.http://www.sciencedirect.com/science/article/pii/S2589004224026968Biological sciencesCell biologyOmicsTranscriptomics
spellingShingle Yiran Song
Li Wang
Haofei Wang
Hong Ma
Jun Xu
Jiandong Liu
Li Qian
Decoding aging in the heart via single cell dual omics of non-cardiomyocytes
iScience
Biological sciences
Cell biology
Omics
Transcriptomics
title Decoding aging in the heart via single cell dual omics of non-cardiomyocytes
title_full Decoding aging in the heart via single cell dual omics of non-cardiomyocytes
title_fullStr Decoding aging in the heart via single cell dual omics of non-cardiomyocytes
title_full_unstemmed Decoding aging in the heart via single cell dual omics of non-cardiomyocytes
title_short Decoding aging in the heart via single cell dual omics of non-cardiomyocytes
title_sort decoding aging in the heart via single cell dual omics of non cardiomyocytes
topic Biological sciences
Cell biology
Omics
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004224026968
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