Evidence map›Paper›PMID 19696409›Full record

ArticleCirculation research2009

iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism.

Almudena Martinez-Fernandez, Timothy J Nelson, Satsuki Yamada, Santiago Reyes, Alexey E Alekseev, Carmen Perez-Terzic, Yasuhiro Ikeda, Andre Terzic

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
8.9field-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

63 citing papers in PubMed, 99 citations in OpenAlex.

  1. Review
  2. Emerging roles of Myc in stem cell biology and novel tumor therapies.Journal of experimental & clinical cancer research : CR · 2018
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. MicroRNAs and Cardiac Regeneration.Circulation research · 2015
    Review
  9. Cardiac regeneration and diabetes.Regenerative medicine research · 2014
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Endogenous cardiac stem cells for the treatment of heart failure.Stem cells and cloning : advances and applications · 2013
    Review
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Almudena Martinez-FernandezMarriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology and Experimental Therapeutics, and Medical Genetics, Mayo Clinic, Rochester, Minn. 55905, USA.
Timothy J Nelson
Satsuki Yamada
Santiago Reyes
Alexey E Alekseev
Carmen Perez-Terzic
Yasuhiro Ikeda
Andre Terzic
Mayo Clinic · US

Funding

CARDIOVASOLOGYT32HL007111 · NHLBI · MAYO CLINIC ROCHESTER · PI Barry A. Borlaug · 1985 to 2026
$8.7M
Regulation of cardiac nuclear pore structure and functionR01HL085208 · NHLBI · MAYO CLINIC ROCHESTER · PI TERZIC, CARMEN MILITZA · 2007 to 2011
$1.9M
Cardioprotective Repair through CardiopoiesisR01HL083439 · NHLBI · MAYO CLINIC ROCHESTER · PI TERZIC, ANDRE · 2006 to 2010
$1.8M
TRIM5alpha-mediated block of HIV-1 productionR56AI074363 · NIAID · MAYO CLINIC ROCHESTER · PI IKEDA, YASUHIRO · 2008 to 2008
$340k
NHLBI NIH HHS R01 HL083439NHLBI NIH HHS R01HL083439NHLBI NIH HHS R01 HL085208NHLBI NIH HHS R01HL085208NHLBI NIH HHS T32 HL007111NHLBI NIH HHS T32HL007111NIAID NIH HHS R56 AI074363NIAID NIH HHS R56AI074363
6 · The paper itself

Abstract

rationaleInduced pluripotent stem cells (iPS) allow derivation of pluripotent progenitors from somatic sources. Originally, iPS were induced by a stemness-related gene set that included the c-MYC oncogene.

objectiveHere, we determined from embryo to adult the cardiogenic proficiency of iPS programmed without c-MYC, a cardiogenicity-associated transcription factor. METHODS AND

resultsTransgenic expression of 3 human stemness factors SOX2, OCT4, and KLF4 here reset murine fibroblasts to the pluripotent ground state. Transduction without c-MYC reversed cellular ultrastructure into a primitive archetype and induced stem cell markers generating 3-germ layers, all qualifiers of acquired pluripotency. Three-factor induced iPS (3F-iPS) clones reproducibly demonstrated cardiac differentiation properties characterized by vigorous beating activity of embryoid bodies and robust expression of cardiac Mef2c, alpha-actinin, connexin43, MLC2a, and troponin I. In vitro isolated iPS-derived cardiomyocytes demonstrated functional excitation-contraction coupling. Chimerism with 3F-iPS derived by morula-stage diploid aggregation was sustained during prenatal heart organogenesis and contributed in vivo to normal cardiac structure and overall performance in adult tumor-free offspring.

conclusionsThus, 3F-iPS bioengineered without c-MYC achieve highest stringency criteria for bona fide cardiogenesis enabling reprogrammed fibroblasts to yield de novo heart tissue compatible with native counterpart throughout embryological development and into adulthood.

Indexed as

Cell TransdifferentiationMyocardial ContractionActininAction PotentialsAnimalsCalcium SignalingCell LineageCells, CulturedChimerismConnexin 43Embryo Culture TechniquesFemaleFibroblastsGene Expression Regulation, DevelopmentalHumansKruppel-Like Factor 4ActininConnexin 43GJA1 protein, mouseKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMef2c protein, mouseMEF2 Transcription FactorsMlc2a protein, mouseMyogenic Regulatory FactorsMyosin Light ChainsOctamer Transcription Factor-3POU5F1 protein, humanProto-Oncogene Proteins c-mycSOX2 protein, humanSOXB1 Transcription FactorsTroponin I

Identifiers

PMID19696409
PMCPMC2785796
OpenAlexW1989312191

What OpenQuestion holds

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LicenceTDM
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.