Transcriptional and Cellular Diversity of the Human Heart

Autor: Kristin G. Ardlie, Nathan R. Tucker, Kenneth B. Margulies, Carolina Roselli, Seung Hoan Choi, Victoria A. Parsons, Christian Stegmann, Caroline N. Herndon, Amelia W. Hall, Patrick T. Ellinor, Stephen J. Fleming, Amer-Denis Akkad, Alessandro Arduini, Mehrtash Babadi, Kenneth Bedi, Irinna Papangeli, François Aguet, Mark Chaffin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Transcription
Genetic
Cell
030204 cardiovascular system & hematology
Genome
Transcriptome
0302 clinical medicine
cardiovascular disease
Gene expression
Adipocytes
Medicine
Homeostasis
Myocytes
Cardiac
RNA-Seq
0303 health sciences
Sex Characteristics
HERITABILITY
Heart
ASSOCIATION
Microfluidic Analytical Techniques
Middle Aged
STEP
medicine.anatomical_structure
Single-Cell Analysis
Cardiology and Cardiovascular Medicine
EXPRESSION
Adult
Cell type
Heart Diseases
Heart Ventricles
Myocytes
Smooth Muscle
Computational biology
Biology
Article
03 medical and health sciences
Physiology (medical)
Humans
Heart Atria
Gene
Genetic association
030304 developmental biology
Aged
IDENTIFICATION
business.industry
Macrophages
Myocardium
RNA
Human heart
Endothelial Cells
Cardiovascular Agents
Fibroblasts
Lymphocyte Subsets
Gene Ontology
Single cell sequencing
business
Pericytes
030217 neurology & neurosurgery
Function (biology)
Zdroj: Circulation
Circulation, 142(5), 466-482. LIPPINCOTT WILLIAMS & WILKINS
ISSN: 0009-7322
Popis: Background: The human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to increase our understanding of cardiac homeostasis and pathology. As recent advances in low-input RNA sequencing have allowed definitions of cellular transcriptomes at single-cell resolution at scale, we have applied these approaches to assess the cellular and transcriptional diversity of the nonfailing human heart. Methods: Microfluidic encapsulation and barcoding was used to perform single nuclear RNA sequencing with samples from 7 human donors, selected for their absence of overt cardiac disease. Individual nuclear transcriptomes were then clustered based on transcriptional profiles of highly variable genes. These clusters were used as the basis for between-chamber and between-sex differential gene expression analyses and intersection with genetic and pharmacologic data. Results: We sequenced the transcriptomes of 287 269 single cardiac nuclei, revealing 9 major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses include 2 distinct groups of resident macrophages, 4 endothelial subtypes, and 2 fibroblast subsets. Comparisons of cellular transcriptomes by cardiac chamber or sex reveal diversity not only in cardiomyocyte transcriptional programs but also in subtypes involved in extracellular matrix remodeling and vascularization. Using genetic association data, we identified strong enrichment for the role of cell subtypes in cardiac traits and diseases. Intersection of our data set with genes on cardiac clinical testing panels and the druggable genome reveals striking patterns of cellular specificity. Conclusions: Using large-scale single nuclei RNA sequencing, we defined the transcriptional and cellular diversity in the normal human heart. Our identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases.
Databáze: OpenAIRE
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