Human pluripotent stem cell (hPSC)-derived progenies (ChIP-Seq)
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ABSTRACT:
PROVIDER: PRJNA695011 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human pluripotent stem cell (hPSC)-derived progenies
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Project description:Human pluripotent stem cell (hPSC)-derived progenies (scRNA-Seq)
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Project description:Human pluripotent stem cell (hPSC)-derived progenies (RNA-Seq)
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Project description:The in vitro culture of human cardiac progenitor cells remains a major challenge in biomedicine. The molecular identity of hPSC-derived cardiac progenies and mechanisms controlling their proliferation and differentiation remain unclear. Here, we show that chromatin remodeling and WNT pathway modulation by chemical inhibitors (IQ-1 and CHIR, respectively) synergistically enables stabilization of human cardiac progenitors (SCPs), in a process of transcriptional uncoupling. SCPs are characterized by ISL1pos/KI-67pos/NKX2-5neg expression and are maintained in a quiescent state in the presence of the inhibitors. Upon compound removal, cell autonomous NKX2-5 upregulation hallmarks the recoupling to the cardiomyogenic program, whilst directed differentiation generates endothelial and smooth muscle cells. Chip-sequencing revealed a narrowly defined open chromatin state in SCPs and, when combined with single cell transcriptome analyses, showed a yet unreported Cardiac Neural Crest Cells (CNCCs) footprint. Enforced expression of the oncogene c-MYC could notably not overcome SCPs proliferative quiescence but disrupted the cell autonomous cardiomyogenic potential instead. In contrast, Retinoic Acid (RA) stimulates SCPs proliferation and further supports cells’ phenotypic homogeneity. We consequently show that our in vitro established treatment with IQ1 can also retain ISL1pos cardiac progenies in vivo in a dose and stage specific manner during zebrafish heart development. Due to its chemically defined and reversible nature, our approach provides an unprecedented opportunity to dissect the key mechanisms in cardiac progenitor cell biology, providing a new tool for the advancement of human heart regeneration.
2025-01-27 | GSE165588 | GEO
Project description:The in vitro culture of human cardiac progenitor cells remains a major challenge in biomedicine. The molecular identity of hPSC-derived cardiac progenies and mechanisms controlling their proliferation and differentiation remain unclear. Here, we show that chromatin remodeling and WNT pathway modulation by chemical inhibitors (IQ-1 and CHIR, respectively) synergistically enables stabilization of human cardiac progenitors (SCPs), in a process of transcriptional uncoupling. SCPs are characterized by ISL1pos/KI-67pos/NKX2-5neg expression and are maintained in a quiescent state in the presence of the inhibitors. Upon compound removal, cell autonomous NKX2-5 upregulation hallmarks the recoupling to the cardiomyogenic program, whilst directed differentiation generates endothelial and smooth muscle cells. Chip-sequencing revealed a narrowly defined open chromatin state in SCPs and, when combined with single cell transcriptome analyses, showed a yet unreported Cardiac Neural Crest Cells (CNCCs) footprint. Enforced expression of the oncogene c-MYC could notably not overcome SCPs proliferative quiescence but disrupted the cell autonomous cardiomyogenic potential instead. In contrast, Retinoic Acid (RA) stimulates SCPs proliferation and further supports cells’ phenotypic homogeneity. We consequently show that our in vitro established treatment with IQ1 can also retain ISL1pos cardiac progenies in vivo in a dose and stage specific manner during zebrafish heart development. Due to its chemically defined and reversible nature, our approach provides an unprecedented opportunity to dissect the key mechanisms in cardiac progenitor cell biology, providing a new tool for the advancement of human heart regeneration.
2025-01-27 | GSE165590 | GEO
Project description:The in vitro culture of human cardiac progenitor cells remains a major challenge in biomedicine. The molecular identity of hPSC-derived cardiac progenies and mechanisms controlling their proliferation and differentiation remain unclear. Here, we show that chromatin remodeling and WNT pathway modulation by chemical inhibitors (IQ-1 and CHIR, respectively) synergistically enables stabilization of human cardiac progenitors (SCPs), in a process of transcriptional uncoupling. SCPs are characterized by ISL1pos/KI-67pos/NKX2-5neg expression and are maintained in a quiescent state in the presence of the inhibitors. Upon compound removal, cell autonomous NKX2-5 upregulation hallmarks the recoupling to the cardiomyogenic program, whilst directed differentiation generates endothelial and smooth muscle cells. Chip-sequencing revealed a narrowly defined open chromatin state in SCPs and, when combined with single cell transcriptome analyses, showed a yet unreported Cardiac Neural Crest Cells (CNCCs) footprint. Enforced expression of the oncogene c-MYC could notably not overcome SCPs proliferative quiescence but disrupted the cell autonomous cardiomyogenic potential instead. In contrast, Retinoic Acid (RA) stimulates SCPs proliferation and further supports cells’ phenotypic homogeneity. We consequently show that our in vitro established treatment with IQ1 can also retain ISL1pos cardiac progenies in vivo in a dose and stage specific manner during zebrafish heart development. Due to its chemically defined and reversible nature, our approach provides an unprecedented opportunity to dissect the key mechanisms in cardiac progenitor cell biology, providing a new tool for the advancement of human heart regeneration.
2025-01-27 | GSE165589 | GEO
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-27 | GSE165591 | GEO
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
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