Evidence map›Paper›PMID 31087611›Full record

ArticleStem cells (Dayton, Ohio)2019

Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation.

Mitch Biermann, Wenxuan Cai, Di Lang, Jack Hermsen, Luke Profio, Ying Zhou, Andras Czirok, Dona G Isai, Brett N Napiwocki, Adriana M Rodriguez and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

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

  1. Pooled it
  2. Immune modulation promotes heart regeneration through macrophage and Granulin functions in medaka.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. The past, present, and future promise of pluripotent stem cells.Journal of immunology and regenerative medicine · 2024
    Article
  7. Article
  8. Article
  9. Rig1 receptor plays a critical role in cardiac reprogramming via YY1 signaling.American journal of physiology. Cell physiology · 2023
    Article
  10. Review
  11. Cardiomyocyte Maturation-the Road is not Obstructed.Stem cell reviews and reports · 2022
    Review
  12. Article
  13. Hematopoietic Stem Cells and Regeneration.Cold Spring Harbor perspectives in biology · 2022
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review
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

21 authors at 4 institutions in 1 country.

Mitch BiermannDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Wenxuan CaiDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Di LangDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jack HermsenDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Luke ProfioDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ying ZhouDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Andras CzirokDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Dona G IsaiDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Brett N NapiwockiDepartment of Engineering Physics, University of Wisconsin-Madison, Madison, Wisconsin.
Adriana M RodriguezDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Matthew E BrownDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Marites T WoonDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Annie ShaoDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Tianxiao HanDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Donglim ParkDepartment of Virology, Harvard University, Boston, Massachusetts, USA.
Timothy A HackerDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Wendy C CroneDepartment of Engineering Physics, University of Wisconsin-Madison, Madison, Wisconsin.
William J BurlinghamDepartment of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Alexey V GlukhovDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ying GeDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Timothy J KampDepartment of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0003-2103-7876
University of Wisconsin–Madison · USUniversity of Wisconsin System · USUniversity of Kansas Medical Center · USHarvard University · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
NRSA Training CoreTL1TR002375 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI Vivek Prabhakaran · 2017 to 2026
$8.4M
Integrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7M
Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
Natural vs. Pathogenic Th17 responses to col Va1, Ka1tubulin and vimentinR01AI119140 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI SULLIVAN, JEREMY A · 2016 to 2020
$1.9M
Refining Cardiac Progenitor Cells for Myocardial RepairR01HL129798 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI KAMP, TIMOTHY J. · 2015 to 2018
$1.5M
University of Wisconsin Transplant Reseach Training ProgramT32AI125231 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KAUFMAN, DIXON B · 2016 to 2020
$1.2M
Morphogenetic Tissue Movements in Early EmbryosR01GM102801 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI CZIROK, ANDRAS · 2014 to 2017
$1.1M
Olympus FV1000 Livecell Confocal SystemS10RR025644 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI KAMP, TIMOTHY J. · 2011 to 2011
$433k
Detection of IL35+ Exosomes as a Marker for Peripheral ToleranceR03AI146688 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI FOLEY, DAVID PAUL · 2020 to 2021
$155k
Isolating Ventricular Progenitor Cells with an Irx4 Reporter, Nanoflares, and Domain AntibodiesF30HL126452 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI BIERMANN, MITCH · 2016 to 2019
$125k
American Heart Association-American Stroke Association 15PRE2577004NCATS NIH HHS TL1 TR002375NCI NIH HHS P30 CA086862NCRR NIH HHS S10 RR025644NHLBI NIH HHS F30 HL126452NHLBI NIH HHS R01 HL129798NHLBI NIH HHS U01 HL134764NIAID NIH HHS R01 AI119140NIAID NIH HHS R03 AI146688NIAID NIH HHS T32 AI125231NIGMS NIH HHS R01 GM102801NIGMS NIH HHS T32 GM008688NIGMS NIH HHS T32 GM008692
6 · The paper itself

Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs (>80% KDR+/PDGFRα+), expression of common cardiac transcription factors, or final purity of differentiated hPSC-CMs (∼90%). However, CPC differentiation in basal medium revealed that pIC priming resulted in hPSC-CMs with enhanced maturity manifested by increased cell size, greater contractility, faster electrical upstrokes, increased oxidative metabolism, and more mature sarcomeric structure and composition. To investigate the mechanisms of CPC priming, RNAseq revealed that cardiac progenitor-stage pIC modulated early Notch signaling and cardiomyogenic transcriptional programs. Chromatin immunoprecipitation of CPCs showed that pIC treatment increased deposition of the H3K9ac activating epigenetic mark at core promoters of cardiac myofilament genes and the Notch ligand, JAG1. Inhibition of Notch signaling blocked the effects of pIC on differentiation and cardiomyocyte maturation. Furthermore, primed CPCs showed more robust formation of hPSC-CMs grafts when transplanted to the NSGW mouse kidney capsule. Overall, epigenetic modulation of CPCs with pIC accelerates cardiomyocyte maturation enabling basic research applications and potential therapeutic uses. Stem Cells 2019;37:910-923.

Indexed as

Epigenesis, GeneticAnimalsCell DifferentiationCell SizeHistonesHumansInduced Pluripotent Stem CellsJagged-1 ProteinKidneyMiceMyocytes, CardiacOxidative PhosphorylationPoly I-CReceptor, Platelet-Derived Growth Factor alphaReceptors, NotchSarcomeresHistonesJAG1 protein, humanJagged-1 ProteinKDR protein, humanPoly I-CReceptor, Platelet-Derived Growth Factor alphaReceptors, NotchVascular Endothelial Growth Factor Receptor-2Cardiac progenitor cellsCardiomyocyte maturationEpigeneticsHuman pluripotent stem cellsNotch signaling

Identifiers

PMID31087611
PMCPMC6599574
OpenAlexW2945577827

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.