Evidence map›Paper›PMID 32810435›Full record

ArticleCell stem cell2020

Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome.

Yifei Miao, Lei Tian, Marcy Martin, Sharon L Paige, Francisco X Galdos, Jibiao Li, Alyssa Klein, Hao Zhang, Ning Ma, Yuning Wei and 13 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
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

114 citing papers in PubMed, 166 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Multimodal Nomogram for the Prenatal Risk Assessment of Hypoplastic Left Heart Syndrome Using Self-Supervised Learning.Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Is There a Unified Etiology of Hypoplastic Left Heart Syndrome? Evaluating Genetic, Structural, and Hemodynamic Models of Disease Initiation.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Defects inFrontiers in genetics · 2026
    Article

54 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

23 authors at 9 institutions in 3 countries.

Yifei MiaoDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine, CuSTOM, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Lei TianStanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Marcy MartinDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.
Sharon L PaigeDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Francisco X GaldosDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Jibiao LiSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Alyssa KleinDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.
Hao ZhangStanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Ning MaStanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Yuning WeiCenter for Personal Dynamic Regulomes, Stanford School of Medicine, Stanford, CA 94305, USA.
Maria StewartPerinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine, CuSTOM, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Soah LeeDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Jan-Renier MoonenDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.
Bing ZhangKey Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Xin Hua Hospital, Shanghai Jiao Tong University, Shanghai 200240, China.
Paul GrossfeldDepartment of Pediatrics, UCSD School of Medicine, La Jolla, CA 92093, USA.
Seema MitalDepartment of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada.
David ChitayatDepartment of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada; The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada.
Joseph C WuStanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Marlene RabinovitchDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA.
Timothy J NelsonDivision of General Internal Medicine, Division of Pediatric Cardiology, and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Shuyi NieSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Sean M WuDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Institute of Stem Cell and Regenerative Biology, Stanford School of Medicine, Stanford, CA 94305, USA.
Mingxia GuDepartment of Pediatrics, Division of Pediatric Cardiology, Stanford School of Medicine, Stanford, CA 94305, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford School of Medicine, Stanford, CA 94305, USA; Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine, CuSTOM, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: mingxia.gu@cchmc.org.
Stanford Medicine · USCalifornia Institute for Regenerative Medicine · USCincinnati Children's Hospital Medical Center · USGeorgia Institute of Technology · USHospital for Sick Children · CAMayo Clinic · USShanghai Jiao Tong University · CNUniversity of California, San Diego · USUniversity of Toronto · CA

Funding

LABORATORY OF DEVELOPMENTAL BIOLOGYR24HD000836 · NICHD · UNIVERSITY OF WASHINGTON · PI Ian Amos Glass · 1995 to 2026
$16.9M
Enabling Technologies for Human-Machine Hybrid TissuesDP1LM012179 · NLM · STANFORD UNIVERSITY · PI WU, SEAN M · 2014 to 2018
$3.8M
NICHD NIH HHS R24 HD000836NLM NIH HHS DP1 LM012179
6 · The paper itself

Abstract

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by abnormalities in the left ventricle, associated valves, and ascending aorta. Studies have shown intrinsic myocardial defects but do not sufficiently explain developmental defects in the endocardial-derived cardiac valve, septum, and vasculature. Here, we identify a developmentally impaired endocardial population in HLHS through single-cell RNA profiling of hiPSC-derived endocardium and human fetal heart tissue with an underdeveloped left ventricle. Intrinsic endocardial defects contribute to abnormal endothelial-to-mesenchymal transition, NOTCH signaling, and extracellular matrix organization, key factors in valve formation. Endocardial abnormalities cause reduced cardiomyocyte proliferation and maturation by disrupting fibronectin-integrin signaling, consistent with recently described de novo HLHS mutations associated with abnormal endocardial gene and fibronectin regulation. Together, these results reveal a critical role for endocardium in HLHS etiology and provide a rationale for considering endocardial function in regenerative strategies.

Indexed as

Hypoplastic Left Heart SyndromeInduced Pluripotent Stem CellsEndocardiumHumansMyocardiumSignal Transductionde novo mutationendocardiumendothelial to mesenchymal transitionETS1fibronectinhuman heart tissuehypoplastic left heart syndromeinduced pluripotent stem cellsNOTCHsingle-cell RNA-seq

Identifiers

PMID32810435
PMCPMC7541479
OpenAlexW3049056316

What OpenQuestion holds

Textmetadata
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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.