Tissue-resident memory T cells- iPSC-cardiomyocyte co-cultures
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE256520 | GEO | 2024/07/19
REPOSITORIES: GEO
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Project description:Tissue-resident memory T cells- iPSC-cardiomyocyte co-cultures
| PRJNA1079821 | ENA
Project description:Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treatable with antiarrhythmic drugs, but patient responses are highly variable. Human induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) are useful for discovering precision therapeutics, but current platforms yield an immature cellular phenotype and are not easily scalable for high-throughput screening. Here, we report that primary adult atrial, but not ventricular, fibroblasts induced greater functional iPSC-aCM maturation, partly through connexin-40 and ephrin-B1 signaling. We developed a protein patterning process within industry-standard multiwell plates to engineer patterned co-culture (PC) of iPSC-aCMs and atrial fibroblasts that significantly enhanced iPSC-aCM structural, electrical, contractile, and metabolic maturation for 6+ weeks versus conventional mono-/co-cultures. PC displayed greater sensitivity for detecting drug efficacy than monocultures, and enabled the modeling and pharmacological or gene editing treatment of an AF-like electrophysiological phenotype due to a sodium channel mutation. In conclusion, PC is useful to elucidate heterotypic cell signaling in the atria, drug screening, and to model AF.
2024-01-19 | GSE239321 | GEO
Project description:Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treatable with antiarrhythmic drugs, but patient responses are highly variable. Human induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) are useful for discovering precision therapeutics, but current platforms yield an immature cellular phenotype and are not easily scalable for high-throughput screening. Here, we report that primary adult atrial, but not ventricular, fibroblasts induced greater functional iPSC-aCM maturation, partly through connexin-40 and ephrin-B1 signaling. We developed a protein patterning process within industry-standard multiwell plates to engineer patterned co-culture (PC) of iPSC-aCMs and atrial fibroblasts that significantly enhanced iPSC-aCM structural, electrical, contractile, and metabolic maturation for 6+ weeks versus conventional mono-/co-cultures. PC displayed greater sensitivity for detecting drug efficacy than monocultures, and enabled the modeling and pharmacological or gene editing treatment of an AF-like electrophysiological phenotype due to a sodium channel mutation. In conclusion, PC is useful to elucidate heterotypic cell signaling in the atria, drug screening, and to model AF.
2024-01-19 | GSE239317 | GEO
Project description:Despite efforts to mature human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) for disease modeling and high throughput screening, cells remain immature and may not reflect adult biology. Recent advancements utilize electro-mechanical and paracrine stimulation to functionally mature cardiomyocytes, but the resulting engineered constructs continue to lack a microenvironment conducive to electrical signal propagation and maturity. Conductive polymers are attractive candidates to facilitate electrical communication between gaps in sparse hPSC-CM clusters or between hPSC-CMs to repair conduction defects. To create a conductive polymer platform for improved electrical signal propagation between hPSC-CMs and achieve electrical maturity, we electrospun poly(3,4-ethylendioxythiophene):polystyrene sulfonate (PEDOT:PSS) blended with 8% (w/v) poly(vinyl alcohol) (PVA). Matrix fiber structure remained stable over 4 weeks in buffer, stiffness remains near cardiac stiffness in vivo, and electrical conductivity scaled with PEDOT:PSS concentration. When fibroblasts were added to fibers, cells had higher initial attachment to PEDOT:PSS compared to PVA-only scaffolds, and after 5 days, over 90% of fibroblasts remained viable on PEDOT:PSS scaffolds compared to PVA-only scaffolds. Electrically excitable hPSC-CMs cultured on conductive substrates exhibited an upregulation of cardiac and muscle-related genes as opposed to non-conductive substrates. These cells further displayed increased desmoplakin (DP) localization on conductive scaffolds, indicating an improvement in the mechanical stability of our hPSC-CMs. Sarcomere organization also scaled with increasing PEDOT:PSS concentration, even in sub-monolayer cell densities, suggesting that improved organization of the contractile machinery in these cells was due to the electrical condition of the matrix. Calcium handling indicated higher calcium flux with a shorter time to peak, further suggesting improved electrical maturity, even when sub-confluent. Taken together, these data suggest that PEDOT:PSS/PVA scaffolds are stable, of a stiffness relevant to cardiomyocytes, and supportive of electrical coupling even in the absence of a monolayer, which may improve cardiac disease modeling and drug development.
2023-12-13 | GSE226541 | GEO
Project description:Rationale: Monitoring and controlling cardiomyocyte activity with optogenetic tools offers exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level. Objective: To test the hypothesis that cardiomyocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electrical activity in isolated cardiomyocytes and the whole heart as well as function and maturity in induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Methods and Results: We first generated mice with cardiomyocyte-restricted expression of VSFP2.3 and demonstrated distinct sarcolemmal localization of VSFP2.3 without any signs for associated pathologies (assessed by echocardiography). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch-clamping. The utility of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiomyocytes. Optical cardiograms (OCGs) could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in iPSC-derived cardiomyocytes. Conclusions: We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof-of-concept for its utility in optogenetic sensing of physiological and pathological excitation in mature and immature cardiomyocytes in vitro and in vivo. Determination of transgene (VSFP2.3) cardiotoxicity
2015-09-02 | E-GEOD-69190 | biostudies-arrayexpress
Project description:By contrast with mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of spared cardiomyocytes. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. While it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. In this study, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin-1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration. Deep sequencing of isolated single epicardial cells
2015-12-15 | E-GEOD-75583 | biostudies-arrayexpress
Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes. hiPSC-CM in larger islands showed electrical and calcium dynamics indicative of greater functional maturity. We then compared transcriptional signatures of the small and large islands against a developmental time course of cardiac differentiation. Although island size had little effect on expression of most genes whose levels differed between hiPSC-CM and adult primary CM, we identified a subset of genes for which island size drove the majority (58%) of the changes associated with functional maturation. Finally, we patterned hiPSC-CM on islands with a variety of shapes to probe the relative contributions of soluble factors, electrical coupling, and direct cell-cell contacts to the functional maturation. Collectively, our data show that optical electrophysiology is a powerful tool for assaying hiPSC-CM maturation, and that island size powerfully drives activation of a subset of genes involved in cardiac maturation.
2017-06-06 | GSE95296 | GEO
Project description:Evaluate the change in transcription factors that have a role in human mesenchymal stem cell (hMSC) commitment to a cardiomyocyte lineage when co-cultured for 4 days with rat neonatal cardiomyocytes and before acquiring a recognizable cardiac phenotype. A myocardial microenvironment was generated by dissociating neonatal rat hearts and establishing cardiomyocyte primary cultures. HumanMSCs constitutively labeled with dsRed localized to the cell's mitochondria were either grown separately (control) or added to the cardiomyocyte primary cultures and grown for 4 days. dsRed fluorescent hMSCs were harvested from co-cultures at 4 days using a FACscan flow cytometer. The RNA for the microarray analysis was prepared from three biologically separate samples of hMSCs co-cultured for 4 days and from hMSCs grown separately for 4 days (control).
2011-09-15 | E-GEOD-32171 | biostudies-arrayexpress
Project description:Analysis of the effect of electrical field stimulation frequency at the gene expression level. Electrical stimulation has been shown to mature nascent cardiomyocytes and alter their beating properties. The purpose of the array was to identify potential mediators of these effects. Total RNA was isolated from cardiomyocytes subjected to 0.5 Hz, 1 Hz, or 2 Hz continuous electrical stimulation for 7 days, compared to an unstimulated control. Three samples from each group were analyzed
2015-11-05 | E-GEOD-74669 | biostudies-arrayexpress
Project description:Evaluate the change in transcription factors that have a role in human mesenchymal stem cell (hMSC) commitment to a cardiomyocyte lineage when co-cultured for 4 days with rat neonatal cardiomyocytes and before acquiring a recognizable cardiac phenotype.
2011-09-16 | GSE32171 | GEO