Evidence map›Paper›PMID 36563664›Full record

ArticleCell2022

Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease.

Mohamed Ameen, Laksshman Sundaram, Mengcheng Shen, Abhimanyu Banerjee, Soumya Kundu, Surag Nair, Anna Shcherbina, Mingxia Gu, Kitchener D Wilson, Avyay Varadarajan and 10 more

Open access · greenAbstract read
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Hypertensive mt. tRNARedox biology · 2026
    Article
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  11. Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026
    Review
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  15. Article
  16. Review
  17. Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  18. Article
  19. Article
  20. Review

18 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

20 authors at 7 institutions in 1 country.

Mohamed AmeenDepartment of Cancer Biology, Stanford University, Stanford, CA, USA; Illumina Artificial Intelligence Laboratory, Illumina Inc, Foster City, CA, USA.
Laksshman SundaramDepartment of Computer Science, Stanford University, Stanford, CA, USA; Illumina Artificial Intelligence Laboratory, Illumina Inc, Foster City, CA, USA.
Mengcheng ShenCardiovascular Institute, Stanford University, Stanford, CA, USA.
Abhimanyu BanerjeeIllumina Artificial Intelligence Laboratory, Illumina Inc, Foster City, CA, USA; Department of Physics, Stanford University, Stanford, CA, USA.
Soumya KunduDepartment of Computer Science, Stanford University, Stanford, CA, USA.
Surag NairDepartment of Computer Science, Stanford University, Stanford, CA, USA.
Anna ShcherbinaDepartment of Biomedical Informatics, Stanford University, Stanford, CA, USA.
Mingxia GuCenter for Stem Cell and Organoid Medicine, CuSTOM, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kitchener D WilsonCardiovascular Institute, Stanford University, Stanford, CA, USA.
Avyay VaradarajanDepartment of Computer Science, California Institute of Technology, Pasadena, CA, USA.
Nirmal VadgamaDepartment of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
Akshay BalsubramaniDepartment of Genetics, Stanford University, Stanford, CA, USA.
Joseph C WuCardiovascular Institute, Stanford University, Stanford, CA, USA.
Jesse M EngreitzDepartment of Genetics, Stanford University, Stanford, CA, USA.
Kyle FarhIllumina Artificial Intelligence Laboratory, Illumina Inc, Foster City, CA, USA.
Ioannis KarakikesCardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA. Electronic address: ioannis1@stanford.edu.
Kevin C WangDepartment of Cancer Biology, Stanford University, Stanford, CA, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA. Electronic address: kevwang@stanford.edu.
Thomas QuertermousDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: tomq1@stanford.edu.
William J GreenleafDepartment of Genetics, Stanford University, Stanford, CA, USA; Department of Applied Physics, Stanford University, Stanford, CA, USA. Electronic address: wjg@stanford.edu.
Anshul KundajeDepartment of Computer Science, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA. Electronic address: akundaje@stanford.edu.
Stanford University · USCardiovascular Institute of the South · USIllumina (United States) · USCalifornia Institute of Technology · USCincinnati Children's Hospital Medical Center · USStanford Medicine · USVA Palo Alto Health Care System · US

Funding

VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
PRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOMEUM1HG009442 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2017 to 2021
$20.1M
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
Stanford Center for Connecting DNA Variants to Function and PhenotypeUM1HG011972 · NHGRI · STANFORD UNIVERSITY · PI JESSE M ENGREITZ, THOMAS QUERTERMOUS · 2021 to 2026
$10.5M
Causal variant association mechanisms in TCF21 binding coronary disease lociR01HL134817 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2017 to 2026
$6.2M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
Unraveling the pathogenesis of familial dilated cardiomyopathy towards precision medicineR01HL139679 · NHLBI · STANFORD UNIVERSITY · PI Ioannis Karakikes · 2018 to 2026
$4.2M
Predicting context-specific molecular and phenotypic effects of genetic variation through the lens of the cis-regulatory codeU01HG012069 · NHGRI · STANFORD UNIVERSITY · PI Anshul Kundaje · 2021 to 2026
$3.9M
The SMAD3 signaling network in coronary artery disease riskR01HL139478 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2018 to 2026
$3.7M
PDGFD regulates a transcriptional network to modulate smooth muscle cell transition and coronary artery disease riskR01HL156846 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2021 to 2024
$2.7M
Identifying tobacco-genetic interactions through study of the aryl hydrocarbon receptor pathway.R01HL151535 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2021 to 2024
$2.7M
Deep learning frameworks for regulatory genomics.DP2GM123485 · NIGMS · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL · 2016 to 2016
$2.4M
NHGRI NIH HHS R35 HG011324NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS U01 HG012069NHGRI NIH HHS UM1 HG009436NHGRI NIH HHS UM1 HG009442NHGRI NIH HHS UM1 HG011972NHLBI NIH HHS K08 HL119251NHLBI NIH HHS K99 HL135258NHLBI NIH HHS R01 HL134817NHLBI NIH HHS R01 HL139478NHLBI NIH HHS R01 HL139679NHLBI NIH HHS R01 HL145708NHLBI NIH HHS R01 HL150414NHLBI NIH HHS R01 HL151535NHLBI NIH HHS R01 HL156846NHLBI NIH HHS R01 HL171045NIAID NIH HHS U19 AI057266NIAMS NIH HHS R61 AR076815NIGMS NIH HHS DP2 GM123485NIGMS NIH HHS R01 GM136737NIH HHS S10 OD018220NIH HHS S10 OD021763NIH HHS S10 OD025212
6 · The paper itself

Abstract

To define the multi-cellular epigenomic and transcriptional landscape of cardiac cellular development, we generated single-cell chromatin accessibility maps of human fetal heart tissues. We identified eight major differentiation trajectories involving primary cardiac cell types, each associated with dynamic transcription factor (TF) activity signatures. We contrasted regulatory landscapes of iPSC-derived cardiac cell types and their in vivo counterparts, which enabled optimization of in vitro differentiation of epicardial cells. Further, we interpreted sequence based deep learning models of cell-type-resolved chromatin accessibility profiles to decipher underlying TF motif lexicons. De novo mutations predicted to affect chromatin accessibility in arterial endothelium were enriched in congenital heart disease (CHD) cases vs. controls. In vitro studies in iPSCs validated the functional impact of identified variation on the predicted developmental cell types. This work thus defines the cell-type-resolved cis-regulatory sequence determinants of heart development and identifies disruption of cell type-specific regulatory elements in CHD.

Indexed as

ChromatinHeart Defects, CongenitalHeartHumansMutationSingle-Cell AnalysisChromatin

Identifiers

PMID36563664
PMCPMC10122433
OpenAlexW4312211397

What OpenQuestion holds

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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.