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Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation

ABSTRACT: Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation

PROVIDER: PRJNA780111 | ENA |

REPOSITORIES: ENA

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Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [gene]

Project description:Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [gene]

| PRJNA779996 | ENA

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [miRNA]

Project description:Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [miRNA]

| PRJNA780000 | ENA

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation.

Project description:BackgroundHuman-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising disease model, even though hiPSC-CMs cultured for extended periods display an undifferentiated transcriptional landscape. MiRNA-target gene interactions contribute to fine-tuning the genetic program governing cardiac maturation and may uncover critical pathways to be targeted.MethodsWe analyzed a hiPSC-CM public dataset to identify time-regulated miRNA-target gene interactions based on three logical steps of filtering. We validated this process in silico using 14 human and mouse public datasets, and further confirmed the findings by sampling seven time points over a 30-day protocol with a hiPSC-CM clone developed in our laboratory. We then added miRNA mimics from the top eight miRNAs candidates in three cell clones in two different moments of cardiac specification and maturation to assess their impact on differentiation characteristics including proliferation, sarcomere structure, contractility, and calcium handling.ResultsWe uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20,543 transcripts through 120 days of hiPSC-CM differentiation and selected 16 genes and 25 miRNAs based on the inverse pattern of expression (Pearson R-values < - 0.5) and consistency in different datasets. We validated 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < - 0.5) during hiPSC-CMs differentiation and used miRNAs mimics to verify proliferation, structural and functional features related to maturation. We also demonstrated that miR-124 affects Ca2+ handling altering features associated with hiPSC-CMs maturation.ConclusionWe uncovered time-regulated transcripts influencing pathways affecting cardiac differentiation/maturation axis and showed that the top-scoring miRNAs indeed affect primarily structural features highlighting their role in the hiPSC-CM maturation.

| S-EPMC9438174 | biostudies-literature

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [miRNA]

Project description:Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are a promising disease model, although hPSC-CMs are not fully mature cardiomyocytes. We examined exponential differentially expressed miRNA/gene to identify critical time-regulated transcripts associated with hPSC-CM differentiation. We uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20.543 transcripts during the 120 days of hPSC-CM differentiation. We found 16 genes and 26 miRNAs with an inverse pattern of expression (Pearson R-values < -0.5) validated using several human and mouse databases. We further validated these findings using two hPSC-CM lines and seven sampling times over a 30-day protocol and observed 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < -0.5) changing over time. Finally, we tested the top eight miRNAs by adding miRNA mimics to differentiating hPSC-CMs and found that they influenced proliferation and maturation phenotypes. These time-regulated transcripts appear to regulate single or multiple pathways affecting cardiac differentiation.

2022-09-15 | GSE188731 | GEO

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation [gene]

2022-09-15 | GSE188725 | GEO

Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation

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

2022-09-15 | GSE188749 | GEO

RNA sequencing for human induced pluripotent stem cell cardiomyocyte differentiation

Project description:We apply short-read RNA sequencing technology to identify transcripts expressed during four time points of a human induced pluripotent stem cell derived cardiomyocyte differentiation protocol, corresponding to pluripotent, mesoderm, early cardiomyocyte, and cardiomyocyte cell stages. The RNA-seq reads are used to generate custom protein sequence database for proteogenomic applications and downstream mass spectrometry analysis. We demonstrate that this custom RNA-seq-guided proteomics approach can be used to identify protein isoforms that are differentially regulated during cardiac differentiation.

2019-11-15 | GSE137920 | GEO

Light regulates nuclear detainment of intron-retained transcripts through COP1-spliceosome to modulate photomorphogenesis

Project description:Intron retention (IR) is the most common alternative splicing (AS) event in Arabidopsis. Increasing studies have demonstrated a major role of IR in gene expression regulation. The impacts of IR on plant growth and development, and response to environments remains under explored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through detainment of the intron-retained transcripts (IRTs) in the nucleus. Through this mechanism, nuclear-retained IRTs can be kept away from translation. COP1-dependent light modulation of IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in responding to changing light conditions. Further, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggests that light regulates the activity of the spliceosome and the consequent IRTs nucleus detainment to modulate photomorphogenesis through COP1.

2024-05-20 | PXD043190 | Pride

Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish

Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.

2020-07-13 | PXD016235 | Pride

Comparison of cardiomyocyte transcripts after knockdown of Gata4 in zebrafish embryos

Project description:The Gata4 transcription factor is essential for normal heart development, but the molecular basis for its function remain poorly understood. We profiled at the whole genome level transcript changes in cardiomyocytes when Gata4 is depleted from zebrafish embryos. Our objective was to elucidate the cardiomyocyte-specific molecular program functioning downstream of Gata4 in order to better understand the role of Gata4 in cardiac morphogenesis. Six samples in total are deposited. Three replicate control samples and three replicate Gata4 morphant samples were analyzed.

2014-02-06 | E-GEOD-44233 | biostudies-arrayexpress

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