Evidence map›Paper›PMID 34767749›Full record

ArticleStem cell reports2021

Upregulation of the JAK-STAT pathway promotes maturation of human embryonic stem cell-derived cardiomyocytes.

Beatrice Xuan Ho, Hongbing Yu, Jeremy Kah Sheng Pang, Jin-Hui Hor, Lee Chuen Liew, Piotr Szyniarowski, Christina Ying Yan Lim, Omer An, Henry He Yang, Colin L Stewart and 3 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 46% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. 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
  5. Article
  6. Article
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

13 authors at 2 institutions in 1 country.

Beatrice Xuan HoDisease Modeling and Therapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Hongbing YuDisease Modeling and Therapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
Jeremy Kah Sheng PangDisease Modeling and Therapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Jin-Hui HorNeurotherapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
Lee Chuen LiewDisease Modeling and Therapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
Piotr SzyniarowskiA∗STAR Skin Research Labs, 8A Biomedical Grove #06-40, Immunos, Singapore 138648.
Christina Ying Yan LimDisease Modeling and Therapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
Omer AnCancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Henry He YangCancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Colin L StewartA∗STAR Skin Research Labs, 8A Biomedical Grove #06-40, Immunos, Singapore 138648.
Woon Khiong ChanDepartment of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Shi-Yan NgNeurotherapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Physiology, National University of Singapore, 2 Medical Dr, Singapore 117593, Singapore; National Neuroscience Institute, Singapore 308433, Singapore. Electronic address: syng@imcb.a-star.edu.sg.
Boon-Seng SohDisease Modeling and Therapeutics Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore. Electronic address: bssoh@imcb.a-star.edu.sg.
Agency for Science, Technology and Research · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The immature characteristics and metabolic phenotypes of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) restrict their applications for disease modeling, drug discovery, and cell-based therapy. Leveraging on the metabolic shifts from glycolysis to fatty acid oxidation as CMs mature, a human hexokinase1-GFP metabolic reporter cell line (H7 HK1-GFP) was generated to facilitate the isolation of fetal or more matured hPSC-CMs. RNA sequencing of fetal versus more matured CMs uncovered a potential role of interferon-signaling pathway in regulating CM maturation. Indeed, IFN-γ-treated CMs resulted in an upregulation of the JAK-STAT pathway, which was found to be associated with increased expression of CM maturation genes, shift from MYH6 to MYH7 expression, and improved sarcomeric structure. Functionally, IFN-γ-treated CMs exhibited a more matured electrophysiological profile, such as increased calcium dynamics and action potential upstroke velocity, demonstrated through calcium imaging and MEA. Expectedly, the functional improvements were nullified with a JAK-STAT inhibitor, ruxolitinib.

Indexed as

Cell DifferentiationSignal TransductionUp-RegulationCell LineCRISPR-Cas SystemsElectrophysiological PhenomenaGenes, ReporterGreen Fluorescent ProteinsHuman Embryonic Stem CellsHumansInterferon-gammaJanus KinasesMyocytes, CardiacSTAT Transcription FactorsGreen Fluorescent ProteinsInterferon-gammaJanus KinasesSTAT Transcription Factorscardiomyocyte maturationelectrophysiologyJAK-STAT pathwayRNA sequencingstem cell differentiation

Identifiers

PMID34767749
PMCPMC8693666
OpenAlexW3211600397

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.