Evidence map›Paper›PMID 39222876›Full record

ArticleJournal of molecular and cellular cardiology2024

Integrated multi-omics analysis identifies features that predict human pluripotent stem cell-derived progenitor differentiation to cardiomyocytes.

Aaron D Simmons, Claudia Baumann, Xiangyu Zhang, Timothy J Kamp, Rabindranath De La Fuente, Sean P Palecek

Abstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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  5. 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

6 authors.

Aaron D SimmonsDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Claudia BaumannDepartment of Physiology and Pharmacology, and Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
Xiangyu ZhangDepartment of Physiology and Pharmacology, and Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
Timothy J KampDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
Rabindranath De La FuenteDepartment of Physiology and Pharmacology, and Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
Sean P PalecekDepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: sppalecek@wisc.edu.

Funding

Biotechnology Training ProgramT32GM135066 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SCOTT M. COYLE, BRIAN G FOX · 2020 to 2026
$7.0M
A Multi-Omics Approach to Discover Metabolic Critical Quality Attributes for Cardiomyocyte BiomanufacturingR01HL148059 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI PALECEK, SEAN P · 2019 to 2022
$1.5M
Role of the DNA Helicase LSH in female meiosisR56HD093383 · NICHD · UNIVERSITY OF GEORGIA · PI DE LA FUENTE, RABINDRANATH · 2018 to 2018
$300k
NHLBI NIH HHS R01 HL148059NICHD NIH HHS R56 HD093383NIGMS NIH HHS T32 GM135066
6 · The paper itself

Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are advancing cardiovascular development and disease modeling, drug testing, and regenerative therapies. However, hPSC-CM production is hindered by significant variability in the differentiation process. Establishment of early quality markers to monitor lineage progression and predict terminal differentiation outcomes would address this robustness and reproducibility roadblock in hPSC-CM production. An integrated transcriptomic and epigenomic analysis assesses how attributes of the cardiac progenitor cell (CPC) affect CM differentiation outcome. Resulting analysis identifies predictive markers of CPCs that give rise to high purity CM batches, including TTN, TRIM55, DGKI, MEF2C, MAB21L2, MYL7, LDB3, SLC7A11, and CALD1. Predictive models developed from these genes provide high accuracy in determining terminal CM purities at the CPC stage. Further, insights into mechanisms of batch failure and dominant non-CM cell types generated in failed batches are elucidated. Namely EMT, MAPK, and WNT signaling emerge as significant drivers of batch divergence, giving rise to off-target populations of fibroblasts/mural cells, skeletal myocytes, epicardial cells, and a non-CPC SLC7A11+ subpopulation. This study demonstrates how integrated multi-omic analysis of progenitor cells can identify quality attributes of that progenitor and predict differentiation outcomes, thereby improving differentiation protocols and increasing process robustness.

Indexed as

Cell DifferentiationMyocytes, CardiacPluripotent Stem CellsBiomarkersEpigenomicsGene Expression ProfilingHumansMultiomicsTranscriptomeBiomarkersCardiac progenitor cellsCardiomyocytesDifferentiationEpigenomicsHuman pluripotent stem cellsMulti-omicsTranscriptomics

Identifiers

PMID39222876
PMCPMC11534572

What OpenQuestion holds

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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.