Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

1 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 1000

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

ABSTRACT: 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).

INSTRUMENT(S): timsTOF Pro, solariX

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Ying Ge

PROVIDER: MSV000088010 | MassIVE | Sun Aug 22 18:59:00 BST 2021

SECONDARY ACCESSION(S): PXD028055

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Similar Datasets

GNPS 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 | GNPS

Advanced physiological maturation of iPSC-derived human cardiomyocytes using an algorithm-directed optimization of defined media components

Project description:Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold tremendous promise for in vitro modeling to assess native myocardial function and disease mechanisms as well as testing drug safety and efficacy. However, current iPSC-CMs are functionally immature, resembling in vivo CMs of fetal or neonatal developmental states. The use of targeted culture media and organoid formats have been identified as potential high-yield contributors to improve CM maturation. This study presents a novel iPSC-CM maturation medium formulation, designed using a differential evolutionary approach with oxidative capacity as an objective metric for iterative optimization. Relative to gold-standard reference formulations, our approach significantly matured morphology, Ca2+ handling, electrophysiology, and metabolism, which was further validated by multi-omic screening, for cells in either pure or co-cultured microtissue formats. Together, these findings not only provide a reliable workflow for highly functional iPSC-CMs for downstream use, but also demonstrate the power of high-dimensional optimization processes in evoking advanced biological function in vitro.

2022-10-05 | GSE214617 | GEO

RNA-seq analysis of diploid and tetraploid neonatal rat cardiomyocytes

Project description:In response to pathological stress such as congenital heart disease and heart valvular disease, cardiomyocytes (CMs) generally increased the content of DNA and the number of nuclear. This process named CM polyploidization and multi-nucleation, result in the presence of multi-nucleated polyploid CM. However, the significance of multi-nucleated polyploid CM (M*Pc CM) for heart disease remains enigmatic. We speculated that the process of CM polyploidization and multinucleation may be an adaptative response, which may help CM function recovery and survive the stress condition. We sought to determine the mechanism of enhanced mitophagy in M*Pc CMs during hypoxia adaptation.

2021-03-23 | GSE123322 | 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

Comparative gene expression analyses reveal distinct molecular signature between differentially reprogrammed cardiomyocytes

Project description:Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes, iCMs) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CM and iCM are still unknown. Here we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status while iCMs exhibit maturation status that more resemble adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis while iCMs utilize fatty acid oxidation as the main pathway. Importantly, iPSC-CMs and iCMs exhibit different cell cycle status, alteration of which influenced their maturation. Therefore, our study provides a foundation for understanding the pros and cons of different reprogramming approaches.

2017-09-26 | GSE99814 | GEO

Genome-wide transcriptomes of adult mouse cardiomyocytes (CMs) with ectopic expression of reprogramming factors

Project description:We carried out bulk RNA sequencing of normal adult mouse CMs (Control-CMs) and adult mouse CMs with ectopic overexpression of Yamanaka factors (Oct4, Sox2, Klf4, Myc, OSKM-CMs), based on a hypothesis that OSKM would induce at least partial CM dedifferentiation in vivo. More than 2,000 genes were differentially expressed between Control- and OSKM-CMs, which were enriched for gene ontology (GO) terms related to multiple key aspects of CM dedifferentiation. This study provides a genome-wide transcriptional profile of dedifferentiating CMs induced by OSKM.

2024-04-09 | GSE172192 | GEO

Dynamic changes of mRNA expression during development of human embryonic stem cells derived cardiomyocytes

Project description:To dissect complex regulatory mechanisms on cardiac development, we performed the time-series gene expression experiments of human embryonic stem cells (ESCs) differentiated to cardiomyocytes (CMs). The RNA-sequencing at 4 stages of human to CM maturation, representing timepoints with days 15, 30, 45 and 60 of ESC-CMs. The early CMs from differentiation days (D) 0-15 are commonly considered to be immature and embryonic-like. We define late CMs after D15. During this phase, the cells stop dividing and undergo some degree of maturation. This study established distinct dynamic expression patterns of mRNAs/genes and identified several subsets of up- or down-regulated genes with similar expression patterns during CM differentiation and maturation.

2023-08-07 | GSE239918 | 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 induces metabolic maturation in 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.

2021-11-01 | GSE160987 | GEO

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data