Effect of pH modulation on cardiomyocyte differentiation
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ABSTRACT:
PROVIDER: PRJNA869458 | ENA |
REPOSITORIES: ENA
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2024-08-08 | GSE211196 | GEO
Project description:The differentiation to cardiomyocytes is a prerequisite and an important part of heart development. A good understanding of the complicated cardiomyocyte differentiation process benefits cardiogenesis study. Embryonic stem cells (ESCs), cell lines with infinite ability to proliferate and to be differentiated into all cell types of the adult body, are important research tools for investigation of differentiation and meanwhile good models for developmental research. In the current study, genome-wide gene expression of ESCs is profiled through high throughput platform during cardiomyocyte-specific differentiation and maturation. Gene expression patterns of undifferentiated ESCs and ESC-derived cardiomyocytes provide a global overview of genes involved in cardiomyocyte-specific differentiation, whereas marker gene expression profiles of both ESC-related genes and cardiac-specific genes presented the expression pattern shift during differentiation in a pure ESC-derived cardiomyocyte cell culture system. Transgenic mouse ESC clone with M-NM-1-MHCM-bM-^@M-^SPacM-bM-^@M-^SIRESM-bM-^@M-^SEGFP vector containing the EGFP gene and the PuromycinR (Pac) cassette under control of the cardiac M-NM-1-myosin heavy chain (M-NM-1-MHC) promoter was cultured and induced into differentiation. Puromycin was applied after differentiation start to enable cardiomyocyte-specific differentiation. Cells were harvested at 4 time points after differentiation start (day0, day12, day19 and day26). Two biological replicates were taken for every time point.
2014-09-25 | E-GEOD-58300 | biostudies-arrayexpress
Project description:Pten's function in regulating cardiomyocyte differentiation
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Project description:The differentiation to cardiomyocytes is a prerequisite and an important part of heart development. A good understanding of the complicated cardiomyocyte differentiation process benefits cardiogenesis study. Embryonic stem cells (ESCs), cell lines with infinite ability to proliferate and to be differentiated into all cell types of the adult body, are important research tools for investigation of differentiation and meanwhile good models for developmental research. In the current study, genome-wide gene expression of ESCs is profiled through high throughput platform during cardiomyocyte-specific differentiation and maturation. Gene expression patterns of undifferentiated ESCs and ESC-derived cardiomyocytes provide a global overview of genes involved in cardiomyocyte-specific differentiation, whereas marker gene expression profiles of both ESC-related genes and cardiac-specific genes presented the expression pattern shift during differentiation in a pure ESC-derived cardiomyocyte cell culture system.
2014-09-25 | GSE58300 | GEO
Project description:Exposure to per- and polyfluoroalkyl substances (PFASs) such as perfluorooctanesulfonic acid (PFOS) has been associated with congenital heart disease (CHD) and decreased birth weight. PFAS exposure can disrupt signaling pathways relevant for cardiac development in stem cell derived cardiomyocyte assays, including PFOS-induced disruption to in vitro cardiac differentiation into contracting spheroids of cardiomyocytes; the PluriBeat assay. Notably, cell line origin can affect how the assay respond to PFAS exposure. Herein, we examine the effect of PFOS on cardiomyocyte differentiation by transcriptomics profiling of two different human induced pluripotent stem cell (hiPSC) lines, to see if they exhibit a common pattern of disruption. Two stages of differentiation, the cardiac progenitor stage (early) and the cardiomyocyte stage (late), were investigated.
2022-05-03 | GSE202077 | GEO
Project description:We aim to compare the genomic discrepancies across de novo Ph+ ALL, Ph+ MPAL and Ph+ AML, three diseases characterized by the occurrence of BCR-ABL1 transcripts but showing varied immunophenotypes. The data we are now submitting is the genomic copy number variants of these three groups. The following is the abstract with associated manuscript. The chromosome abnormality of Philadelphia (Ph) is typically seen in de novo acute lymphoblastic leukemia (ALL). It has also been identified in mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) in the revisions to World Health Organization classification of myeloid neoplasms and actue leukemia. The discrepancies between these patients and potential mechanisms underlying differentiation fate of the leukemia cells remain poorly defined. We evaluated the clinical, genomic and transcriptomic features of Ph+ ALL, Ph+ MPAL and Ph+ AML by taking advantage of high-density genomic analysis, including next-generation sequencing array comparative genomic hybridization and gene expression profiling for transcriptomic analysis. Our results showed that the three cohorts demonstrated diversified clinical features. Ph+ ALL had the best response to induction therapy, with a complete remission (CR) rate of 93.5 and molecular response of 43.5%. Ph+ MPAL had a 90.0% CR rate but only 5.9% of molecular response. The CR rate of Ph+ AML was only 68.8%. Ph+ ALL was characterized by loss and mutations of B-cell development gene IKZF1 and PAX5, and frequent histone H3K36 trimethyltransferase SETD2 mutations. SETD2 mutations were detected in 11.3% of Ph+ ALL patients and predicted higher relapse rate. Ph+ MPAL and Ph+ AML featured high frequency of RUNX1 mutations. Further studies showed RUNX1-R177X mutation inhibited 32D cell differentiation induced by G-Csf, and cooperated with BCR-ABL1 to lead to myeloid differentiation arrest of human cord blood CD34+ cells. It is therefore presumed that these additional mutations work in synergy with BCR-ABL1 fusion gene to facilitate the development of Ph-positive acute leukemia in different immunophenotypic classifications.
2022-04-29 | GSE130484 | GEO
Project description:Tridimensional cardiac differentiation from hiPSCs has been largely described in the literature. However, the exact impact that 3D culture has throughout the entire process of cardiac differentiation remains poorly defined. We developed a robust and efficient 3D platform for cardiomyocyte differentiation from hiPSCs, based on the temporal modulation of WNT signalling using small molecules. 3D aggregates of hiPSCs were generated by forced aggregation in microwells and subsequently differentiated. In order to determine the differences in gene expression profile due to 3D culture throughout the different stages of cardiac differentiation, we compared transcriptional changes between cells in 3D aggregates and standard 2D monolayer cardiac differentiation. Analysis of these data suggests a faster commitment of hiPSCs toward the cardiac lineage and also higher degree of cardiomyocyte functional maturation after 20 days of culture in the 3D aggregates when compared with the 2D monolayer.
2019-06-24 | GSE116574 | GEO
Project description:Rationale: In virtually all models of heart failure, prognosis is determined by right ventricular (RV) function; thus, understanding the cellular mechanisms contributing to RV dysfunction is critical. Whole organ remodeling is associated with cell-specific changes, including cardiomyocyte dedifferentiation and activation of cardiac fibroblasts (Cfib) which in turn is linked to disorganization of cytoskeletal proteins and loss of sarcomeric structures. However, how these cellular changes contribute to RV function remains unknown. We’ve previously shown significant organ-level RV dysfunction in a large animal model of pulmonary hypertension (PH) which was not mirrored by reduced function of isolated cardiomyocytes. We hypothesized that factors produced by the endogenous Cfib contribute to global RV dysfunction by generating a heterogeneous cellular environment populated by dedifferentiated cells. Objective: To determine the effect of Cfib conditioned media (CM) from the PH calf (PH-CM) on adult rat ventricular myocytes (ARVM) in culture. Methods and Results: Brief exposure (<2 days) to PH-CM results in rapid, marked dedifferentiation of ARVM to a neonatal-like phenotype exhibiting spontaneous contractile behavior. Dedifferentiated cells maintain viability for over 30 days with continued expression of cardiomyocyte proteins including TnI and α-actinin yet exhibit myofibroblast characteristics including expression of α-smooth muscle actin. Using a bioinformatics approach to identify factor(s) that contribute to dedifferentiation, we found activation of the PH Cfib results in a unique transcriptome correlating with factors both in the secretome and with activated pathways in the dedifferentiated myocyte. Further, we identified upregulation of periostin in the Cfib and CM, and demonstrate that periostin is sufficient to drive cardiomyocyte dedifferentiation. Conclusions: These data suggest that paracrine factor(s) released by Cfib from the PH calf signal a phenotypic transformation in a population of cardiomyocytes that likely contributes to RV dysfunction. Therapies targeting this process, such as inhibition of periostin, have the potential to prevent RV dysfunction.
2019-07-07 | GSE133904 | GEO
Project description:The purpose of this study was to understand how prevention of serine/threonine protein kinase (STPK) phosphorylation of PrrA impacts PrrA modulation of M. tuberculosis transcriptional response to acidic pH and high chloride levels.
2022-06-23 | GSE199000 | GEO
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