Cardiac organoids for Hypertophic cardiomyopathy
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ABSTRACT:
PROVIDER: PRJNA1098220 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cardiac Organoids for Cardiomyopathy
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Project description:Cardiac Organoids for Modeling Hypertrophic Cardiomyopathy
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Project description:Human cardiac organoids closely replicate the architecture and function of the human heart, offering a potential accurate platform for studying aging cardiomyopathy. Senolytics have shown potential in addressing age-related pathologies. However, their potential to reverse aging-related human cardiomyopathy remains largely unexplored. We employed human iPSC-derived cardiac organoids (hCardioids) to model doxorubicin-induced cardiomyopathy in an aged context. hCardioids were treated with doxorubicin (DOXO) and subsequently with a combination of two senolytics: dasatinib (D) and quercetin (Q). DOXO-treated hCardioids exhibited significantly increased oxidative stress, DNA damage (pH2AX), cellular senescence (p16) and decreased cell proliferation associated with a senescence-associated secretory phenotype (SASP). DOXO-treated hCardioids were considerably deprived of cardiac progenitors and displayed reduced cardiomyocyte proliferation as well as contractility. These distinctive aging-associated characteristics were confirmed by global RNA-sequencing analysis. Treatment with D+Q reversed these effects, reducing oxidative stress and senescence markers, alleviating SASP, and restoring hCardioids viability and function Additionally, senolytics replenished cardiac progenitors and reversed the cardiomyocyte proliferation deficit. Doxorubicin triggers an age-associated phenotype in hCardioids representing a reliable model of aged cardiomyopathy. Senescence is a key mechanism of the aged phenotype as senolytics rejuvenated aged hCardioids restoring their structure and function while reverting the age-associated regenerative deficit.
2026-01-29 | GSE280050 | GEO
Project description:Senolytics rejuvenate aging cardiomyopathy in human cardiac organoids
| PRJNA1176030 | ENA
Project description:BACKGROUND: MYBPC3 is one of the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, the molecular mechanisms of how mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. Thus, advancing in-vitro studies to define these mechanisms of mutations leading to HCM are still warranted. Thus, the primary objective of this study was to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with MYBPC3 mutation utilizing isogenic human-induced pluripotent stem cell (hiPSC)-derived cardiac organoids (hCOs).
2025-01-28 | GSE262876 | GEO
Project description:We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.
| 2090060 | ecrin-mdr-crc
Project description:This study utilized TMT to characterize the cardiac proteomic differences between patients with hypertrophic cardiomyopathy and controls.
2023-04-28 | MSV000091821 | MassIVE
Project description:Cardiac fibroblasts of dilated cardiomyopathy patients
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Project description:Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Lysine demethylase 8 (Kdm8) represses gene expression in the embryo and controls metabolism in cancer. However, its function in cardiac homeostasis is unknown. We show that Kdm8 maintains a mitochondrial gene network active by repressing Tbx15 to prevent dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiates. Moreover, NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration towards heart failure and could underlie heterogeneity of dilated cardiomyopathy.
2022-12-23 | GSE215793 | GEO
Project description:Outcome Spatial molecular imaging to evaluate the difference between organoids generated from WT and D389V mutant carrier.
2025-01-28 | GSE263591 | GEO