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Comparison of FTDP-17 IVS10+16 patient derived hiPSC and ZFN engineered hiPSC

ABSTRACT: Comparison of FTDP-17 IVS10+16 patient derived hiPSC and ZFN engineered hiPSC

PROVIDER: PRJNA415550 | ENA |

REPOSITORIES: ENA

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ZFN engineered hiPSC with the FTDP-17 associated MAPT IVS10+16 mutation w/wo additional P301S mutation and comparison of FTDP-17 IVS10+16 patient derived hiPSC and ZFN engineered hiPSC

Project description:ZFN engineered hiPSC with the FTDP-17 associated MAPT IVS10+16 mutation w/wo additional P301S mutation and comparison of FTDP-17 IVS10+16 patient derived hiPSC and ZFN engineered hiPSC

| PRJNA415549 | ENA

ZFN engineered hiPSC with the FTDP-17 associated MAPT IVS10+16 mutation w/wo additional P301S mutation

Project description:ZFN engineered hiPSC with the FTDP-17 associated MAPT IVS10+16 mutation w/wo additional P301S mutation

| PRJNA407941 | ENA

Comparison of FTDP-17 IVS10+16 patient derived hiPSC and ZFN engineered hiPSC

Project description:The development of an effective therapy against tauopathies like Alzheimer’s disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization. Altogether, these tau mutant iPSC lines allow us to study IVS10+16 and P301S mutations in an isogenic background and to unravel a potential link between pathogenic 4R tau expression and FTDP-17.

2018-08-01 | GSE106075 | GEO

ZFN engineered hiPSC with the FTDP-17 associated MAPT IVS10+16 mutation w/wo additional P301S mutation

2018-08-01 | GSE104013 | GEO

Panicum virgatum cultivar:SAP-17-16

Project description:Panicum virgatum exome capture - SAP-17-16

| PRJNA447753 | ENA

ZFN engineered hiPSC with the FTDP-17 associated MAPT IVS10+16 mutation w/wo additional P301S mutation and comparison of FTDP-17 IVS10+16 patient derived hiPSC and ZFN engineered hiPSC

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-08-01 | GSE106076 | GEO

hiPSC-derived CF proportions in MEW-based human engineered cardiac tissue

Project description:hiPSC-derived CF proportions in MEW-based human engineered cardiac tissue

| PRJNA1400025 | ENA

hiPSC-derived CF proportions in MEW-based human engineered cardiac tissue

Project description:The recapitulation of the physiological cellular composition, 3D structure and mechanics of the human myocardium is key to improving the biofabrication of cardiac tissues. To advance the development of engineered heart patches, with significant potential for human cardiac repair, we assessed the impact of their cellular and extracellular constituents on tissue organization and function, by using advanced biofabrication and next-generation sequencing technologies. Combining melt electrowriting (MEW) fibrillary scaffolds with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts (-CFs), we generated human engineered cardiac tissues (MEW-hECTs) by casting in two different biomaterial compositions (fibrin and gelatin-methacryloyl (GelMA)), and varying proportions of the cardiac constituent cells. Under the conditions tested, fibrin-hECTs displayed improved tissue formation, coordinated contraction, structural organization, and electrophysiological behavior compared with GelMA-hECTs. Transcriptomics analysis indicated that fibrin-hECTs exhibited an increase in maturation-associated gene expression signatures compared with GelMA-hECTs, whereas a longer remodeling process of the synthetic environment was required in GelMA. Surprisingly, within the investigated MEW-based composite system, the inclusion of CFs had no positive impact on tissue organization and impaired the electrophysiological properties of myocardial constructs, increasing susceptibility to arrhythmias in computational simulations calibrated with experimental electrophysiological data. This information will help devise advanced myocardial tissues by enabling a comprehensive assessment of the main components, ultimately reflecting the unique native cardiac 3D organization.

2026-09-08 | GSE315964 | GEO

Contractile work contributes to maturation of energy metabolism in hiPSC-derived cardiomyocytes

Project description:Energy metabolism is a key aspect of cardiomyocyte biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for biomedical application, but they are immature and have not undergone metabolic shift related to early postnatal development. Cultivation of hiPSC-CM in 3D engineered heart tissue (EHT) format leads to morphological maturation. This study compared the mitochondrial and metabolic state of hiPSC-CM in standard 2D culture and the EHT format and determined the influence of contractile activity. HiPSC-CM in EHTs showed ~2-fold higher number of mitochondria (electron microscopy), mitochondrial mass (mitotracker), DNA (Mt-ND1, Mt-ND2), and protein abundance (proteome) than in 2D culture. While hiPSC-CM exhibited the principal ability to use glucose, lactate and fatty acids as energy substrates irrespective of culture format, hiPSC-CM in 3D performed more oxidation of glucose, lactate and fatty acid, and less anaerobic glycolysis. The increase in mitochondrial mass and DNA in 3D was diminished by pharmacological inhibition of contractile force, suggesting that contractile work participates in mitochondrial development hiPSC-CM. In conclusion, contractile work in the EHT format contributes to metabolic maturation of hiPSC-CM.

2018-03-06 | PXD008205 | Pride

Comparative analysis of the cardiomyocyte between 16 day and 140 days after differentiation

Project description:We generate Bulk-RNA sequencing data from two human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) cell lines. The first cell line was harvested 16 days after differentiation (hiPSC-CM-D16); this cell line still actively proliferated. The second cell line was harvested 140 days after differentiation (hiPSC-CM-D140); this cell line ceased proliferation. Comparing the Bulk-RNA sequencing data between these two cell lines may reveal regulators promoting hiPSC-CM proliferation.

2025-02-18 | GSE289839 | GEO

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