Evidence map›Paper›PMID 37014753›Full record

ArticleCell reports2023

Trajectory reconstruction identifies dysregulation of perinatal maturation programs in pluripotent stem cell-derived cardiomyocytes.

Suraj Kannan, Matthew Miyamoto, Renjun Zhu, Michaela Lynott, Jason Guo, Elaine Zhelan Chen, Alexandre R Colas, Brian Leei Lin, Chulan Kwon

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Cardiac maturation.Journal of molecular and cellular cardiology · 2024
    Review
  13. Integrative transcriptomics and cell systems analyses reveal protective pathways controlled by Igfbp-3 in anthracycline-induced cardiotoxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  14. Cross-Organ Transcriptomic Comparison Reveals Universal Factors During Maturation.Journal of computational biology : a journal of computational molecular cell biology · 2022
    Article
  15. 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

9 authors.

Suraj KannanDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Matthew MiyamotoDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Renjun ZhuDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Michaela LynottSanford Burham Prebys Medical Discovery Institute, San Diego, CA, USA.
Jason GuoDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Elaine Zhelan ChenDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Alexandre R ColasSanford Burham Prebys Medical Discovery Institute, San Diego, CA, USA.
Brian Leei LinDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Chulan KwonDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: ckwon13@jhmi.edu.

Funding

Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Transcriptomic Entropy to Quantify Maturation of PSC-Derived CardiomyocytesR01HL156947 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KIM, DEOK-HO, KWON, CHULAN · 2021 to 2024
$2.3M
Engineered Human Heart Slice for Testing Drug-Induced ArrhythmiaR01HL152249 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BOHELER, KENNETH RICHARD, KWON, CHULAN · 2020 to 2022
$2.0M
Discovery of Small Molecule Promoters of Cardiomyocyte Proliferation to Restore Cardiac Performance in DiseaseR01HL148827 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI COLAS, ALEXANDRE ROMAIN · 2019 to 2022
$2.0M
Discovery of small molecule regulators of atrial cardiomyocyte action potential duration to restore normal cardiac rhythm in atrial fibrillationR01HL153645 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI COLAS, ALEXANDRE ROMAIN · 2021 to 2024
$1.9M
TRPC6 inhibition therapy to rescue cardiac muscle dysfunction in muscular dystrophyR00HL155840 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Brian Leei Lin · 2024 to 2026
$747k
TRPC6 inhibition therapy to rescue cardiac muscle dysfunction in muscular dystrophyK99HL155840 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI LIN, BRIAN LEEI · 2022 to 2023
$261k
NHLBI NIH HHS K99 HL155840NHLBI NIH HHS R00 HL155840NHLBI NIH HHS R01 HL148827NHLBI NIH HHS R01 HL152249NHLBI NIH HHS R01 HL153645NHLBI NIH HHS R01 HL156947NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

A limitation in the application of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) is the failure of these cells to achieve full functional maturity. The mechanisms by which directed differentiation differs from endogenous development, leading to consequent PSC-CM maturation arrest, remain unclear. Here, we generate a single-cell RNA sequencing (scRNA-seq) reference of mouse in vivo CM maturation with extensive sampling of previously difficult-to-isolate perinatal time periods. We subsequently generate isogenic embryonic stem cells to create an in vitro scRNA-seq reference of PSC-CM-directed differentiation. Through trajectory reconstruction, we identify an endogenous perinatal maturation program that is poorly recapitulated in vitro. By comparison with published human datasets, we identify a network of nine transcription factors (TFs) whose targets are consistently dysregulated in PSC-CMs across species. Notably, these TFs are only partially activated in common ex vivo approaches to engineer PSC-CM maturation. Our study can be leveraged toward improving the clinical viability of PSC-CMs.

Indexed as

Induced Pluripotent Stem CellsPluripotent Stem CellsAnimalsCell DifferentiationEmbryonic Stem CellsHumansMiceMyocytes, CardiacTranscription FactorsTranscription FactorscardiomyocyteCP: Stem cell researchmaturationsingle-cell RNA sequencingstem cellstissue engineering

Identifiers

PMID37014753
PMCPMC10545814

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.