Evidence map›Paper›PMID 32403949›Full record

ArticleCirculation2020

Transcriptional and Cellular Diversity of the Human Heart.

Nathan R Tucker, Mark Chaffin, Stephen J Fleming, Amelia W Hall, Victoria A Parsons, Kenneth C Bedi, Amer-Denis Akkad, Caroline N Herndon, Alessandro Arduini, Irinna Papangeli and 8 more

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 381 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
381citing papers in PubMed, 3 pooled it
30.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

381 citing papers in PubMed, 3 syntheses or guidelines pooled it, 559 citations in OpenAlex.

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  16. Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.Medical science monitor : international medical journal of experimental and clinical research · 2026
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321 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 3 countries.

Nathan R Tucker *Precision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Mark Chaffin *Precision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Stephen J FlemingPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Amelia W HallPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Victoria A ParsonsCardiovascular Research Center, Massachusetts General Hospital, Boston (N.R.T., A.W.H., V.A.P., P.T.E.).
Kenneth C BediPerelman School of Medicine, University of Pennsylvania, Philadelphia (K.C.B., K.B.M.).
Amer-Denis AkkadPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Caroline N HerndonPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Alessandro ArduiniPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Irinna PapangeliPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Carolina RoselliPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
François AguetThe Broad Institute of MIT and Harvard (F.A., K.G.A.), Cambridge, MA.
Seung Hoan ChoiPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Kristin G ArdlieThe Broad Institute of MIT and Harvard (F.A., K.G.A.), Cambridge, MA.
Mehrtash BabadiPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Kenneth B MarguliesPerelman School of Medicine, University of Pennsylvania, Philadelphia (K.C.B., K.B.M.).
Christian M StegmannPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Patrick T EllinorPrecision Cardiology Laboratory (N.R.T., M.C., S.J.F., A.W.H., A.-D.A., C.N.H., A.A., I.P., C.R., S.H.C., M.B., C.M.S., P.T.E.), Cambridge, MA.
Anna Needs Neuroblastoma Answers · USMassachusetts General Hospital · USPrecision for Medicine (United States) · USBC Platforms (Finland) · FIBroad Institute · USUniversity of Pennsylvania · USParsons (United States) · USUniversity Medical Center Groningen · NL

Funding

IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
Integrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9M
AFGen Consortium: Atrial Fibrillation Genomics to Functional AnalysesR01HL128914 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2015 to 2018
$3.1M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
Defining the functional variation underlying atrial fibrillation riskK01HL140187 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI TUCKER, NATHAN R · 2018 to 2022
$858k
NHLBI NIH HHS K01 HL140187NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105993NHLBI NIH HHS R01 HL128914
6 · The paper itself

Abstract

backgroundThe 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.

methodsMicrofluidic 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.

resultsWe 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.

conclusionsUsing 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.

Indexed as

Transcription, GeneticAdipocytesAdultAgedCardiovascular AgentsEndothelial CellsFibroblastsGene OntologyHeartHeart AtriaHeart DiseasesHeart VentriclesHomeostasisHumansLymphocyte SubsetsMacrophagesCardiovascular Agentscardiovascular diseaseheartRNA

Identifiers

PMID32403949
PMCPMC7666104
OpenAlexW3025989739

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.