Reelin and Thrombospondin1 regulate cardiomyocyte proliferation through Vldlr
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE176009 | GEO | 2021/06/03
REPOSITORIES: GEO
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Project description:Reelin and Thrombospondin1 regulate cardiomyocyte proliferation through Vldlr
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Project description:Human embryonic stem cells (hESCs) can be used to generate scalable numbers of cardiomyocytes for studying cardiac biology, disease modeling, drug screens, and potentially for regenerative therapies. Directed differentiation protocols for cardiomyocytes using hESCs are well established, but methods to isolate highly pure population of cardiomyocytes are limited. Reporter cell lines can be valuable for purification and visualization of cells for such applications. We used CRISPR/Cas9 in hESCs to place an mCherry reporter gene into the MYH6 locus, facilitating a simple method to purify cardiomyocytes. MYH6:mCherry positive cells express atrial and ventricular markers and display a range of cardiomyocyte action potential morphologies. At 20 days of differentiation, MYH6:mCherry+ cells show features characteristic of human cardiomyocytes and can be used successfully to monitor drug-induced cardiotoxicity and oleic acid-induced cardiomyocyte arrhythmia. The MYH6:mCherry hESC reporter line should serve as a useful tool for disease modeling and drug development relevant to cardiomyocyte biology.
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2020-02-24 | E-MTAB-8515 | biostudies-arrayexpress
Project description:We performed RNA-Seq analysis of neoatal rat ventricular cardiomyocytes (NRVCs) and human pluripotent stem cells derived cardiomyocytes (hPSC-CMs) which were treated with Nimodipine (NM) to investigate the moleclular mechanism of inhibiting L-type calcium channel (LTCC) to promote cardiomyocyte proliferation.
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Project description:Analysis of lipid metabolism at gene expression level. Total RNA obtained from isolated retinas from Vldlr ko mice and Jax WT mice
2016-03-14 | E-GEOD-78831 | biostudies-arrayexpress
Project description:We designed microRNA-responsive, modified mRNA switches (miR-switches) that quantitatively control their own translation level by determining the miRNA activities. We found that the three miR-switches (i.e., miR-1-, miR-208-, and miR-499-switches) enable to purify cardiomyocytes differentiated from hPSCs with high efficiency, accuracy, and safety. The purified cardiomyocytes were engrafted in mouse heart and did not form tumor. Simultaneous purification of two different cell types, cardiomyocytes and endothelial cells, was also performed by transfecting the mRNA responding to the both miR-208 and miR-126, into heterogeneous cell population derived from hPSCs. In addition, selective induction of apoptosis in noncardiomyocytes triggered by miR-1/208-Bim switch enriched cardiomyocytes without cell sorting. The mRNA switch could purify desired cell types and control cell death pathways by monitoring the miRNA expression dynamics during cell fate conversion. MYH6-EIP4 iPSCs for mRNA, N=3 MYH6-EIP4 day18 cardiomyocytes (before transfection) for mRNA, N=3 MYH6-EIP4 day19 cardiomyocytes (miR-1-switch day1) for mRNA, N=3 MYH6-EIP4 day19 cardiomyocytes (without transfection) for mRNA, N=3 MYH6-EIP4 day25 cardiomyocytes (miR-1-switch day7) for mRNA, N=3 MYH6-EIP4 day25 cardiomyocytes (without transfection) for mRNA, N=3 201B7 d22 miR-208a-BFP sorted cells for mRNA, N=1 201B7 d22 miR-208a-BFP negative fraction sorted cells for mRNA, N=1 201B7 d22 SIRPA+LIN- sorted cells for mRNA, N=1 201B7 d22 SIRPA+LIN- negative fraction sorted cells for mRNA, N=1 201B7 d22 VCAM1+ sorted cells for mRNA, N=1 201B7 d22 VCAM1+negative fraction sorted cells for mRNA, N=1 MYH6-EIP4 day19 cardiomyocytes (miR-208a-Bim-switch day1) for mRNA, N=1 MYH6-EIP4 day19 cardiomyocytes (without transfection) for mRNA, N=1 MYH6-EIP4 day21 cardiomyocytes (miR-208a-Bim-switch day7) for mRNA, N=1 MYH6-EIP4 day21 cardiomyocytes (without transfection) for mRNA, N=1 MYH6-EIP4 day25 cardiomyocytes (miR-208a-Bim-switch day7) for mRNA, N=1 MYH6-EIP4 day25 cardiomyocytes (without transfection) for mRNA, N=1
2015-05-20 | E-GEOD-60632 | biostudies-arrayexpress
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2015-05-20 | E-GEOD-60633 | biostudies-arrayexpress
Project description:Cardiac hypertrophy is associated with growth and functional changes of cardiomyocytes,including mitochondrial alterations, but the latter are still poorly understood. Here we investigated mitochondrial function and dynamic localization in neonatal rat ventricular cardiomyocytes (NRVCs) stimulated with insulin like growth factor 1 (IGF1) or phenylephrine (PE), mimicking physiological and pathological hypertrophic responses,respectively. A decreased activity of the mitochondrial electron transport chain (ETC) (state 3) was observed in permeabilized NRVCs stimulated with PE, whereas this was improved in IGF1 stimulated NRVCs. In contrast, in intact NRVCs, mitochondrial oxygen consumption rate (OCR) was increased in PE stimulated NRVCs, but remained constant in IGF1 stimulated NRVCs. After stimulation with PE, mitochondria localized to the periphery of the cell. To study the differences in more detail, we performed gene array studies. IGF1 and PE stimulated NRVCs did not reveal major differences in gene expression of mitochondrial encoding proteins, but we identified a gene encoding amotor protein implicated in mitochondrial localization, kinesin family member 5b (Kif5b ), which was clearly elevated in PE stimulated NRVCs but not in IGF1 stimulated NRVCs. We confirmed that Kif5b gene and protein expression was elevated in animal models with pathological cardiac hypertrophy. Silencing of Kif5b reverted the peripheral mitochondrial localization in PE stimulated NRVCs and diminished PE induced increases in mitochondrial OCR, indicating that KIF5B dependent localization affects cellular responses to PE stimulated NRVCs. These results indicate that KIF5B contributes to mitochondrial localization and function in cardiomyocytes and may play a role in pathological hypertrophic responses in vivo.
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Project description:Autophagy plays vital housekeeping neuronal functions but is not believed to fuel energy metabolism. Autophagy regulation by lipids nutrient sensors have not been identified. Cone photoreceptors’ very-low-density lipoprotein receptor (Vldlr) expression facilitates the uptake of triglyceride-derived fatty acid. In Vldlr-/- mice, we identify free fatty acid receptor 1 (Ffar1) as a suppressor of transcription factor EB (Tfeb), a master regulator of autophagy. Tfeb, in turn, governs the expression of PGC1 and Sirtuin-3, leading to reduced -ketoglutarate (-KG). We recently showed that low -KG in Vldlr-/- photoreceptors drives Vegfa expression and neovascularization reminiscent of a subset of age-related macular degeneration (AMD). Metabolomics of human AMD vitreous and Vldlr-/- retinas identified a similar Krebs cycle metabolite signature. Improving autophagy in AMD-like mice rescued the neovascular phenotype and vision. Dysregulated autophagy may therefore compound the energy failure of photoreceptors contributing to neovascular AMD and could be a driving force in other neovascular diseases.
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Project description:The goal of the study was to determine global expression differences and commanlities in three different Reeler mutant mosue models. Phenotypically mice deficient in Reelin, Dab1 or both Reelin receptors apoEr2 and Vldlr exhibit a severe Reeler phenotype. We used microarrays to detail the global programme of gene expression changes occurring in the frontal cortex of three different mouse models which each generate a Reeler phenotype.
2017-02-15 | GSE94896 | GEO