ArticlePloS one2013
Transcriptome-guided functional analyses reveal novel biological properties and regulatory hierarchy of human embryonic stem cell-derived ventricular cardiomyocytes crucial for maturation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Mitochondrial-Targeted Therapy for Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2022Review
- Temporal Control of the WNT Signaling Pathway During Cardiac Differentiation Impacts Upon the Maturation State of Human Pluripotent Stem Cell Derived Cardiomyocytes.Frontiers in molecular biosciences · 2022Article
- Maturing heart muscle cells: Mechanisms and transcriptomic insights.Seminars in cell & developmental biology · 2021Review
- Pathogenesis and drug response of iPSC-derived cardiomyocytes from two Brugada syndrome patients with different NaJournal of biomedical research · 2021Article
- Cell surface markers for immunophenotyping human pluripotent stem cell-derived cardiomyocytes.Pflugers Archiv : European journal of physiology · 2021Review
- AMPKβ1 and AMPKβ2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification.The Journal of biological chemistry · 2020Article
- Acid-Sensitive Ion Channels Are Expressed in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Stem cells and development · 2019Article
- Modulation of chromatin remodeling proteins SMYD1 and SMARCD1 promotes contractile function of human pluripotent stem cell-derived ventricular cardiomyocyte in 3D-engineered cardiac tissues.Scientific reports · 2019Article
- Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2019Article
- Structural and Mechanistic Bases of Nuclear Calcium Signaling in Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes.Stem cells international · 2019Article
- Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.Circulation. Genomic and precision medicine · 2018Article
- Article
- An integrative method to decode regulatory logics in gene transcription.Nature communications · 2017Article
- Same-Single-Cell Analysis of Pacemaker-Specific Markers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Subtypes Classified by Electrophysiology.Stem cells (Dayton, Ohio) · 2016Article
- Phospholamban as a crucial determinant of the inotropic response of human pluripotent stem cell-derived ventricular cardiomyocytes and engineered 3-dimensional tissue constructs.Circulation. Arrhythmia and electrophysiology · 2015Article
- Article
- Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2014Review
- High efficiency differentiation of human pluripotent stem cells to cardiomyocytes and characterization by flow cytometry.Journal of visualized experiments : JoVE · 2014Article
- Developmental cues for the maturation of metabolic, electrophysiological and calcium handling properties of human pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2014Review
- Survey of network-based approaches to research of cardiovascular diseases.BioMed research international · 2014Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human (h) embryonic stem cells (ESC) represent an unlimited source of cardiomyocytes (CMs); however, these differentiated cells are immature. Thus far, gene profiling studies have been performed with non-purified or non-chamber specific CMs. Here we took a combinatorial approach of using systems biology to guide functional discoveries of novel biological properties of purified hESC-derived ventricular (V) CMs. We profiled the transcriptomes of hESCs, hESC-, fetal (hF) and adult (hA) VCMs, and showed that hESC-VCMs displayed a unique transcriptomic signature. Not only did a detailed comparison between hESC-VCMs and hF-VCMs confirm known expression changes in metabolic and contractile genes, it further revealed novel differences in genes associated with reactive oxygen species (ROS) metabolism, migration and cell cycle, as well as potassium and calcium ion transport. Following these guides, we functionally confirmed that hESC-VCMs expressed IKATP with immature properties, and were accordingly vulnerable to hypoxia/reoxygenation-induced apoptosis. For mechanistic insights, our coexpression and promoter analyses uncovered a novel transcriptional hierarchy involving select transcription factors (GATA4, HAND1, NKX2.5, PPARGC1A and TCF8), and genes involved in contraction, calcium homeostasis and metabolism. These data highlight novel expression and functional differences between hESC-VCMs and their fetal counterparts, and offer insights into the underlying cell developmental state. These findings may lead to mechanism-based methods for in vitro driven maturation.
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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.