High-resolution transcriptomic profiling of the heart during chronic stress reveals cellular drivers of cardiac fibrosis and hypertrophy
| العنوان: | High-resolution transcriptomic profiling of the heart during chronic stress reveals cellular drivers of cardiac fibrosis and hypertrophy |
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| المؤلفون: | Gabriella E. Farrugia, Nadia A. Rosenthal, Micheal A. McLellan, Daniel A. Skelly, Malathi S.I. Dona, Taylah L. Gaynor, Henry Diep, Galen T. Squiers, Alexander R. Pinto, Raghav Pandey, Charles D. Cohen, Antony Vinh |
| المصدر: | Circulation |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cardiac & Cardiovascular Systems, Cardiac fibrosis, PATHOGENESIS, High resolution, heart failure, 030204 cardiovascular system & hematology, Bioinformatics, ANGIOGENESIS, Muscle hypertrophy, Pathogenesis, Transcriptome, Mice, 0302 clinical medicine, ENDOPLASMIC-RETICULUM STRESS, Fibrosis, Original Research Articles, Medicine, Chronic stress, MACROPHAGES, Pyrophosphatases, 1102 Cardiorespiratory Medicine and Haematology, GENE-EXPRESSION, Uncategorized, 0303 health sciences, education.field_of_study, UNFOLDED PROTEIN RESPONSE, ESTROGEN, Cardiology, cardiovascular system, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, SEX, Single-Cell Analysis, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Myofibroblast, medicine.medical_specialty, Population, Cardiomegaly, 1117 Public Health and Health Services, 03 medical and health sciences, Stress, Physiological, Physiology (medical), Internal medicine, Animals, education, 030304 developmental biology, Science & Technology, business.industry, Gene Expression Profiling, Myocardium, NATIONAL HEART, fibrosis, 1103 Clinical Sciences, Fibroblasts, medicine.disease, Angiotensin II, Peripheral Vascular Disease, Cardiovascular System & Hematology, Heart failure, Cardiovascular System & Cardiology, Thrombospondins, business |
| الوصف: | Supplemental Digital Content is available in the text. Background: Cardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators that drive cardiac fibrosis, and the relative effect of disparate cell populations on cardiac fibrosis, remain unclear. Methods: We developed a novel cardiac single-cell transcriptomic strategy to characterize the cardiac cellulome, the network of cells that forms the heart. This method was used to profile the cardiac cellular ecosystem in response to 2 weeks of continuous administration of angiotensin II, a profibrotic stimulus that drives pathological cardiac remodeling. Results: Our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to pathological remodeling of the extracellular matrix of the heart. Two phenotypically distinct fibroblast populations, Fibroblast-Cilp and Fibroblast-Thbs4, emerged after induction of tissue stress to promote fibrosis in the absence of smooth muscle actin–expressing myofibroblasts, a key profibrotic cell population. After angiotensin II treatment, Fibroblast-Cilp develops as the most abundant fibroblast subpopulation and the predominant fibrogenic cell type. Mapping intercellular communication networks within the heart, we identified key intercellular trophic relationships and shifts in cellular communication after angiotensin II treatment that promote the development of a profibrotic cellular microenvironment. Furthermore, the cellular responses to angiotensin II and the relative abundance of fibrogenic cells were sexually dimorphic. Conclusions: These results offer a valuable resource for exploring the cardiac cellular landscape in health and after chronic cardiovascular stress. These data provide insights into the cellular and molecular mechanisms that promote pathological remodeling of the mammalian heart, highlighting early transcriptional changes that precede chronic cardiac fibrosis. |
| DOI: | 10.1101/854026 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ede146f2cc04847382099c06f56766f https://doi.org/10.1101/854026 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4ede146f2cc04847382099c06f56766f |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.1101/854026 |
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