Evidence map›Paper›PMID 35931076›Full record

ArticleStem cell reports2022

Dual inhibition of MAPK and PI3K/AKT pathways enhances maturation of human iPSC-derived cardiomyocytes.

Bayardo I Garay, Sophie Givens, Phablo Abreu, Man Liu, Doğacan Yücel, June Baik, Noah Stanis, Taylor M Rothermel, Alessandro Magli, Juan E Abrahante and 9 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023
    Pooled it
  2. Article
  3. Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Pluripotent stem cell-based approaches for heart repair and the potential of genetic modifications.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  10. Article
  11. Article
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  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. The Role of Stem Cells in the Treatment of Cardiovascular Diseases.International journal of molecular sciences · 2024
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Bayardo I GarayLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Sophie GivensBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Phablo AbreuLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Man LiuLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Doğacan YücelIntegrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA.
June BaikLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Noah StanisBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Taylor M RothermelBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Alessandro MagliLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Juan E AbrahanteUniversity of Minnesota Informatics Institute, Minneapolis, MN, USA.
Natalya A GolovizninaMolecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, MN, USA; LHI, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Hossam A N SolimanLHI, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Neha R DhokeLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Michael KybaStem Cell Institute, University of Minnesota, Minneapolis, MN, USA; Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, MN, USA; LHI, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Patrick W AlfordBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Samuel C DudleyLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Jop H van BerloLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA; Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA.
Brenda OgleBiomedical Engineering, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Rita R C PerlingeiroLillehei Heart Institute (LHI), Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA; Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, MN, USA. Electronic address: perli032@umn.edu.
University of Minnesota · USMinneapolis Heart Institute Foundation · USUniversity of Minnesota Medical Center · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6M
Probing the Activity of DUX4 in FSHDR01AR055685 · NIAMS · UNIVERSITY OF MINNESOTA · PI Michael Kyba · 2010 to 2026
$7.0M
Training in Mechanisms of Cardiovascular DiseasesT32HL072742 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI TOBACMAN, LARRY S · 2003 to 2013
$3.7M
Na+ channel mRNA splicing in heart failureR01HL104025 · NHLBI · UNIVERSITY OF MINNESOTA · PI DUDLEY, SAMUEL C · 2011 to 2019
$3.3M
Immune Mechanisms Regulating Cardiac RemodelingR01HL155993 · NHLBI · UNIVERSITY OF MINNESOTA · PI REVELO, XAVIER, VAN BERLO, JOHANNES (JOP) · 2021 to 2024
$2.9M
Computational and Experimental Modeling of Cardiomyocyte ProliferationR01HL160665 · NHLBI · UNIVERSITY OF VIRGINIA · PI SAUCERMAN, JEFFREY J., VAN BERLO, JOHANNES (JOP) · 2022 to 2025
$2.8M
Training Program in Cardiac InnovationT32HL144472 · NHLBI · UNIVERSITY OF MINNESOTA · PI Peter A Crawford, SAMUEL C DUDLEY · 2019 to 2026
$2.6M
Skeletal Muscle Regeneration from Pluripotent Stem CellsR01AR078571 · NIAMS · UNIVERSITY OF MINNESOTA · PI PERLINGEIRO, RITA C. R. · 2021 to 2025
$2.1M
Targeting Dystroglycanopathies using Pluripotent-derived Myogenic ProgenitorsR01AR071439 · NIAMS · UNIVERSITY OF MINNESOTA · PI PERLINGEIRO, RITA C. R. · 2017 to 2021
$1.9M
Extracellular matrix regulation of differentiation via modulation of ILK: application to 3D bioprinting of cardiac tissueR01HL137204 · NHLBI · UNIVERSITY OF MINNESOTA · PI MCALPINE, MICHAEL, OGLE, BRENDA M · 2017 to 2020
$1.7M
Metabolic Regulation of Sodium ChannelsR01HL106592 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DUDLEY, SAMUEL C · 2011 to 2014
$1.6M
Understanding the Transcriptional Networks and Physiologic Adaptations Governing the Clinical Manifestations of Duchenne Muscular DystrophyF30HL151138 · NHLBI · UNIVERSITY OF MINNESOTA · PI GARAY, BAYARDO ISIDORE · 2020 to 2023
$202k
NHLBI NIH HHS F30 HL151138NHLBI NIH HHS R01 HL104025NHLBI NIH HHS R01 HL106592NHLBI NIH HHS R01 HL137204NHLBI NIH HHS R01 HL155993NHLBI NIH HHS R01 HL160665NHLBI NIH HHS T32 HL072742NHLBI NIH HHS T32 HL144472NIAMS NIH HHS R01 AR055685NIAMS NIH HHS R01 AR071439NIAMS NIH HHS R01 AR078571NIGMS NIH HHS T32 GM008244
6 · The paper itself

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide great opportunities for mechanistic dissection of human cardiac pathophysiology; however, hiPSC-CMs remain immature relative to the adult heart. To identify novel signaling pathways driving the maturation process during heart development, we analyzed published transcriptional and epigenetic datasets from hiPSC-CMs and prenatal and postnatal human hearts. These analyses revealed that several components of the MAPK and PI3K-AKT pathways are downregulated in the postnatal heart. Here, we show that dual inhibition of these pathways for only 5 days significantly enhances the maturation of day 30 hiPSC-CMs in many domains: hypertrophy, multinucleation, metabolism, T-tubule density, calcium handling, and electrophysiology, many equivalent to day 60 hiPSC-CMs. These data indicate that the MAPK/PI3K/AKT pathways are involved in cardiomyocyte maturation and provide proof of concept for the manipulation of key signaling pathways for optimal hiPSC-CM maturation, a critical aspect of faithful in vitro modeling of cardiac pathologies and subsequent drug discovery.

Indexed as

Induced Pluripotent Stem CellsCell DifferentiationCells, CulturedHumansInfant, NewbornMyocytes, CardiacPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktcalcium handlingcardiomyocyteelectrophysiologyinhibitorsMAPKmaturationmultinucleationPI3K-AKTpluripotent stem cells

Identifiers

PMID35931076
PMCPMC9481895
OpenAlexW4289835520

What OpenQuestion holds

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Registered trials

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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.