Evidence map›Paper›PMID 34534204›Full record

ArticlePLoS computational biology2021

Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.

Suraj Kannan, Michael Farid, Brian L Lin, Matthew Miyamoto, Chulan Kwon

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Single-cell Technology in Stem Cell Research.Current stem cell research & therapy · 2025
    Review
  11. Article
  12. Article
  13. A transcriptional enhancer regulates cardiac maturation.Nature cardiovascular research · 2024
    Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023
    Article
  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

5 authors at 1 institution in 1 country.

Suraj KannanDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine; Baltimore, Maryland, United States of America.ORCID 0000-0002-7820-7381
Michael FaridDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine; Baltimore, Maryland, United States of America.ORCID 0000-0002-6734-9931
Brian L LinDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine; Baltimore, Maryland, United States of America.ORCID 0000-0003-0800-7103
Matthew MiyamotoDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine; Baltimore, Maryland, United States of America.ORCID 0000-0002-2140-6769
Chulan KwonDivision of Cardiology, Department of Medicine, Johns Hopkins School of Medicine; Baltimore, Maryland, United States of America.ORCID 0000-0002-4924-2778
Johns Hopkins University · US

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
NHLBI NIH HHS R01 HL152249NHLBI NIH HHS R01 HL156947NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

The immaturity of pluripotent stem cell (PSC)-derived tissues has emerged as a universal problem for their biomedical applications. While efforts have been made to generate adult-like cells from PSCs, direct benchmarking of PSC-derived tissues against in vivo development has not been established. Thus, maturation status is often assessed on an ad-hoc basis. Single cell RNA-sequencing (scRNA-seq) offers a promising solution, though cross-study comparison is limited by dataset-specific batch effects. Here, we developed a novel approach to quantify PSC-derived cardiomyocyte (CM) maturation through transcriptomic entropy. Transcriptomic entropy is robust across datasets regardless of differences in isolation protocols, library preparation, and other potential batch effects. With this new model, we analyzed over 45 scRNA-seq datasets and over 52,000 CMs, and established a cross-study, cross-species CM maturation reference. This reference enabled us to directly compare PSC-CMs with the in vivo developmental trajectory and thereby to quantify PSC-CM maturation status. We further found that our entropy-based approach can be used for other cell types, including pancreatic beta cells and hepatocytes. Our study presents a biologically relevant and interpretable metric for quantifying PSC-derived tissue maturation, and is extensible to numerous tissue engineering contexts.

Indexed as

BenchmarkingTranscriptomeGene ExpressionHepatocytesHumansInsulin-Secreting CellsMyocytes, CardiacPluripotent Stem CellsSequence Analysis, RNASingle-Cell AnalysisTissue Engineering

Identifiers

PMID34534204
PMCPMC8448341
OpenAlexW3198981533

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.