Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [miRNA]

ABSTRACT: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are a promising disease model, although hPSC-CMs are not fully mature cardiomyocytes. We examined exponential differentially expressed miRNA/gene to identify critical time-regulated transcripts associated with hPSC-CM differentiation. We uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20.543 transcripts during the 120 days of hPSC-CM differentiation. We found 16 genes and 26 miRNAs with an inverse pattern of expression (Pearson R-values < -0.5) validated using several human and mouse databases. We further validated these findings using two hPSC-CM lines and seven sampling times over a 30-day protocol and observed 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < -0.5) changing over time. Finally, we tested the top eight miRNAs by adding miRNA mimics to differentiating hPSC-CMs and found that they influenced proliferation and maturation phenotypes. These time-regulated transcripts appear to regulate single or multiple pathways affecting cardiac differentiation.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE188731 | GEO | 2022/09/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [gene]

Project description:Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are a promising disease model, although hPSC-CMs are not fully mature cardiomyocytes. We examined exponential differentially expressed miRNA/gene to identify critical time-regulated transcripts associated with hPSC-CM differentiation. We uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20.543 transcripts during the 120 days of hPSC-CM differentiation. We found 16 genes and 26 miRNAs with an inverse pattern of expression (Pearson R-values < -0.5) validated using several human and mouse databases. We further validated these findings using two hPSC-CM lines and seven sampling times over a 30-day protocol and observed 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < -0.5) changing over time. Finally, we tested the top eight miRNAs by adding miRNA mimics to differentiating hPSC-CMs and found that they influenced proliferation and maturation phenotypes. These time-regulated transcripts appear to regulate single or multiple pathways affecting cardiac differentiation.

2022-09-15 | GSE188725 | GEO

Metabolomics Identifies Metabolic Markers of Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes

Project description:Cardiovascular disease is a leading cause of death worldwide. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold immense clinical potential and recent studies have enabled generation of virtually pure hPSC-CMs with high efficiency in chemically defined and xeno-free conditions. Despite these advances, hPSC-CMs exhibit an immature phenotype and are arrhythmogenic in vivo, necessitating development of methods to mature these cells. hPSC-CMs undergo significant metabolic alterations during differentiation and maturation. A detailed analysis of the metabolic changes accompanying maturation of hPSC-CMs may prove useful in identifying new strategies to expedite the maturation process and also provide biomarkers for testing or validating hPSC-CM maturation. In this study we identified global metabolic changes which take place during long-term culture and maturation of hPSC-CMs derived from three different hPSC lines. We have identified several metabolic pathways, including phospholipid metabolism and pantothenate and Coenzyme A metabolism, which showed significant enrichment upon maturation in addition to fatty acid oxidation and metabolism. We also identified an increase in glycerophosphocholine and reduction in phosphocholine as potential metabolic biomarkers of maturation. These biomarkers were also affected in a similar manner during murine heart development in vivo. These results support that hPSC-CM maturation is associated with extensive metabolic rewiring and understanding the role of these metabolic changes in maturation process has the potential to develop novel approaches to monitor and expedite hPSC-CM maturation.

2018-04-24 | MTBLS425 | MetaboLights

A Multi-omics Method Enabled by Sequential Metabolomics and Proteomics for Human Pluripotent Stem Cell-derived Cardiomyocytes

Project description:Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show immense promise for patient-specific disease modeling, cardiotoxicity screening, and regenerative therapy development. However, hPSC-CMs in culture have not recapitulated the structural or functional properties of adult CMs in vivo thus far. To gain global insight into hPSC-CM biology, we established a multi-omics method for analyzing the hPSC-CM metabolome and proteome from the same cell culture, creating multi-dimensional profiles of hPSC-CMs. Specifically, we developed a sequential extraction to capture metabolites and proteins from the same hPSC-CM monolayer cultures, and analyzed these extracts using high-resolution mass spectrometry (MS).

2021-08-22 | MSV000088010 | MassIVE

GNPS A Multi-omics Method Enabled by Sequential Metabolomics and Proteomics for Human Pluripotent Stem Cell-derived Cardiomyocytes

2021-08-22 | MSV000088010 | GNPS

Unbiased Proteomics Benchmarking of Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes

Project description:Rationale: Human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) exhibit the properties of fetal CMs, which limit their applications. Various methods have been used to promote maturation of hPSC-CMs; however, there is a lack of an unbiased and comprehensive method for accurate benchmarking of hPSC-CM maturation. Objective: We aim to develop an unbiased proteomics method integrating high-throughput top-down targeted proteomics and bottom-up global proteomics for accurate and comprehensive assessment of hPSC-CM maturation. Methods and Results: Utilizing hPSC-CMs from early- and late-stage two-dimensional monolayer culture and three-dimensional engineered cardiac tissue, we demonstrated high reproducibility and reliability of the top-down proteomics method, which enabled simultaneous quantification of contractile protein isoform expressions and their PTMs. This method allowed for the detection of known maturation-associated contractile protein alterations, and for the first time, identified contractile protein PTMs as promising new markers of maturation. By employing a global proteomics strategy, we identified candidate maturation markers important for sarcomere organization, cardiac excitability, and Ca2+ homeostasis; and validated these markers in the developing mouse cardiac ventricles. Conclusions: We established an unbiased proteomics method that can provide accurate and specific benchmarking of hPSC-CM maturation, and identified new markers of maturation. Furthermore, this integrated proteomics strategy laid a strong foundation for uncovering molecular basis underlying cardiac development and disease using hPSC-CMs.

| MSV000082985 | MassIVE

A transcriptional enhancer regulates cardiac maturation [RNA-seq]

Project description:Cardiomyocyte maturation is crucial for generating adult cardiomyocytes and the application of human pluripotent stem cell derived-cardiomyocytes (hPSC-CMs). However, regulation at the cis-regulatory element level, and its role in heart disease remain unclear. Alpha-actinin 2 (ACTN2) levels increase during CM maturation. Here, we investigate a clinically relevant, conserved ACTN2 enhancer’s effects on CM maturation using hPSC and mouse models. Heterozygous ACTN2 enhancer deletion led to abnormal CM morphology, reduced function, and mitochondrial respiration. Transcriptomic analyses in vitro and in vivo showed disrupted CM maturation and upregulated anabolic mammalian target for rapamycin (mTOR) signaling promoting senescence and hindering maturation. As confirmation, ACTN2 enhancer deletion induced heat shock protein 90A expression, a chaperone mediating mTOR activation. Conversely, targeting the ACTN2 enhancer via enhancer CRISPR activation (enCRISPRa) promoted hPSC-CM maturation. Our studies reveal the transcriptional enhancer’s role in cardiac maturation and disease, offering insights into potentially fine-tuning gene expression to modulate cardiomyocyte physiology.

2024-05-24 | GSE266306 | GEO

A transcriptional enhancer regulates cardiac maturation [scRNA-seq]

2024-05-24 | GSE266307 | GEO

RNA Expression Profiling of Human iPSC-Derived Cardiomyocytes in a Cardiac Hypertrophy Model [mRNA expression]

Project description:Cardiac hypertrophy is an independent risk factor for cardiovascular disease and heart failure. There is increasing evidence that microRNAs (miRNAs) play an important role in the regulation of messenger RNA (mRNA) and the pathogenesis of various cardiovascular diseases. However, the ability to comprehensively study cardiac hypertrophy on a gene regulatory level is impacted by the limited availability of human cardiomyocytes. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer the opportunity for disease modeling. We utilized a previously established in vitro model of cardiac hypertrophy to interrogate the regulatory mechanism associated with the cardiac disease process. We performed miRNA sequencing and mRNA expression analysis on endothelin 1 (ET-1) stimulated hiPSC-CMs to describe associated RNA expression profiles. MicroRNA sequencing revealed over 250 known and 34 predicted novel miRNAs to be differentially expressed between ET-1stimulated and unstimulated control hiPSC-CMs. Messenger RNA expression analysis identified 731 probe sets with significant differential expression. Computational target prediction on significant differentially expressed miRNAs and mRNAs identified nearly 2000 target pairs. To characterize miRNA and mRNA expression patterns we utilized iCell Cardiomyocytes derived from human iPSCs (hiPSC-CMs). Based on preliminary dose-response and time-course studies, we stimulated these cells with ET-1 at 10-8M for 18h. We used unstimulated control (control-CM) and ET-1 stimulated (ET1-CM) hiPSCs from 3 separate experiments as triplicate data for this study. mRNA expression for the control-CM and ET1-CM samples was analyzed using GeneChip 3M-bM-^@M-^YIVT express arrays (Affymetrix).

2014-10-03 | E-GEOD-60291 | biostudies-arrayexpress

PPARdelta signaling activation improves metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes

Project description:Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease. A major caveat however is that they remain functionally and structurally immature in culture, limiting their potential for disease modeling and regenerative approaches. Here we address the question of how different metabolic pathways can be modulated in order to induce efficient cardiac maturation of hPSC-CMs. We show that PPAR signaling acts in an isoform-specific manner to balance the glycolysis and fatty acid oxidation (FAO) pathways. PPARd activation or inhibition results in efficient respective up- or down-regulation of the gene regulatory networks underlying FAO in hPSC-CMs. PPARd induction further increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation and augments FAO flux. Lastly PPARd activation results in enhanced myofibril organization and increased numbers of bi-nucleated hPSC-CMs. Transient lactate exposure, commonly used in hPSC-CM purification protocols, induces an independent program of cardiac maturation, but when combined with PPARd activation equally results in a metabolic switch to FAO. In summary, we identify multiple axes of metabolic modifications of hPSC-CMs including a role for PPARdelta signaling in inducing the metabolic switch to FAO in hPSC-CMs. Our findings provide new opportunities to generate and use metabolically mature hPSC-CMs including for disease modeling and regenerative therapy.

2022-04-09 | GSE178984 | GEO

PPARdelta signaling induces metabolic maturation in human pluripotent stem cell-derived cardiomyocytes

2021-11-01 | GSE160987 | GEO