Genome-wide analysis of day 31 hESC-cardiomyocytes treated with DMSO (control) or retinoic acid (RA) during differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61154 | GEO | 2015/01/01
SECONDARY ACCESSION(S): PRJNA260367
REPOSITORIES: GEO
Similar Datasets
Project description:Human embryonic stem cell-reporter line hESC-NKX2.5(eGFP/w) were differentiated to cardiomyocytes (CMs) by utilizing the spin embryoid body method. During differentiation the cells were treated with DMSO or retinoic acid (RA) from day 4-7. At day 31, cells were sorted based on GFP prior to RNA isolation. The results of this microarray demonstrate that CMs treated with RA during differentiation exhibit atrial-like gene expression profile, while DMSO-treated cells show ventricular-like gene profile. CMs treated with DMSO or RA during differentiation were sorted for GFP and analyzed for differential gene expression.
2015-01-01 | E-GEOD-61154 | biostudies-arrayexpress
Project description:We analyzed anterior halves of NF stage 15 embryos that were treated with 10uM DMSO (control), or 1uM RA and 10uM 4-oxo-RA (experimental) for changes in gene expression induced by the two mophogens. RNA-sequencing revealed significant overlap in genes upregulated by both RA and 4-oxo-RA, and to a lesser extent, those downregulated by them. We report all Zic-1 targets described in accompanying manuscript to be regulated by both RA and 4-oxo-RA.
2022-03-09 | GSE180269 | GEO
Project description:To uncover the mechanism that Wnt signaling modulates RA-induced ESC differentiation, we conducted time course RNA-seq analysis during the differentiation. Transcriptome profiles of RA-induced and RA/CHIR-induced ESC differentiation were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000. The RNA-seq data revealed a significant decrease in mesoderm (one of the major source of vascular SMCs) markers and increase in PrE markers in CHIR treated samples, while other lineage markers showed no significant expression, implying a diverging to PrE fate by Wnt activation. Subsequent hierarchical clustering analysis also showed that the gene expression profiles of cells derived from RA induction alone clustered with adult SMCs, while cells derived from RA/CHIR induction gradually clustered to XEN cells with differentiation and was very close to XEN cells at day 16, suggesting that RA/CHIR-induced ESCs differentiated into PrE lineage. This study provided new insights into the importance of RA/Wnt crosstalk in the lineage differentiation of ESCs.
2019-12-10 | GSE123632 | GEO
Project description:Rhodothermaceae bacterium RA strain:RA Genome sequencing
| PRJNA308615 | ENA
Project description:Background: Cardiomyocytes (CMs) induced from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocytes. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart and high concentrations of RA have been shown to steer differentiation towards atrial CMs, whereas lower concentrations of RA promote a more ventricular-like CM profile. Aim: Create engineered heart tissue (EHT) with left and right ventricular phenotype from hiPSCs by intervening with specific concentrations of retinoic acid (RA) during hiPSC differentiation towards CM. Methods: hiPSC were derived by reprogramming skin fibroblasts. Different concentrations of RA (Control group without RA, LRA group with 0.05 µM and HRA group with 0.1 µM) were administered during third to sixth days of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling CMs derived from hiPSC (hiPSC-CM) at high cell density in a low collagen hydrogel. The maturation and growth of EHTs were induced in a customized biomimetic tissue culture system, that provides continuous electrical stimulation, medium agitation and stretch. The function of CMs and EHTs was analyzed under different conditions. Finally, RNA extraction and tissue fixation were performed on CMs and EHTs for RT-qPRC and immunofluorescence staining analysis. RNA sequencing was conducted on EHTs to examine how RA affects both the function and structure of EHT. Results: In the HRA group, hiPSC-CMs exhibited the first onset of beating and showed the highest expression of maturity genes MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are the marker genes for left ventricular CMs, was also the highest in the HRA group. The transcription factor MEF2C associated with RA and ventricular development genes, NPPA and MYH7, were highly expressed in the HRA group, while GATA4 was less expressed in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was more functionally similar to the left ventricle. The expression of TBX5 and NKX2.5 was found to be the highest expression in the HRA group of EHT, while expression of TBX20 and ISL1 was found to be the highest expression in control group. When the electrical stimulation frequency of EHT in the HRA group was raised, it correspondingly increased its contractile force. The heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA. Conclusion: By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHT with a phenotype similar to that of the left ventricle or right ventricle. Our research paved the way for future studies on in vitro left ventricular or right ventricular function, personalized drug screening, and precision medicine.
2023-10-25 | GSE245954 | GEO
Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
2020-10-15 | PXD005911 | Pride
Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
2016-07-05 | PXD004357 | Pride
Project description:NT2 cells were treated with DMSO (control) or 10uM Retinoic Acid (RA). Total RNA was isolated using TriReagent, and subsequent cleanup with RNeasy columns (Qiagen) according to the manufacturer's directions. Hybridizations were performed according to Affymetrix guidelines using the Human HG-U133A chip containing 22,500 unique genetic elements. Double-stranded cDNA was synthesized using Superscript II RT (Invitrogen). In vitro transcription labeling was performed with biotin labeled nucleotides using the Bioarray High Yield RNA Labeling Kit (ENZO). 20 ul of labeled RNA per sample was added to the hybridization cocktail, with a total of 15 ug hybridized to the chip (16 hours, 45C). RMA analysis was performed using Gene Traffic software (Iobion), where raw data for each hybridization was normalized, background corrected and filtered for signal intensity of 50 or greater in at least one comparison. Keywords: other
2005-10-18 | GSE2448 | GEO
Project description:Coordinated transcriptional and epigenetic mechanisms that direct development of the later differentiating second heart field (SHF) progenitors remain largely unknown. Here, we show that a novel zebrafish histone deacetylase 1 (hdac1) mutant allele cardiac really gone (crg) has a deficit of ventricular CMs and smooth muscle within the outflow tract (OFT) due to both cell and non-cell autonomous loss in SHF progenitor proliferation. Cyp26-deficient embryos, which have increased retinoic acid (RA) levels, have similar defects in SHF-derived OFT development. We found that nkx2.5+ progenitors from hdac1 and cyp26-deficient embryos have ectopic expression of ripply3, a transcriptional co-repressor of T-box transcription factors that is normally restricted to the posterior pharyngeal endoderm. Furthermore, the ripply3 expression domain is expanded anteriorly into the posterior nkx2.5+ progenitor domain in crg mutants. Importantly, excess ripply3 is sufficient to repress VC development, while genetic depletion of Ripply3 and Tbx1 in crg mutants can partially restore VC number. We find that in crg mutants the epigenetic signature at RA response elements (RAREs) that can associate with Hdac1 and RA receptors (RARs) becomes indicative of transcriptional activation. Our study highlights that transcriptional repression via the epigenetic regulator Hdac1 facilitates OFT development through directly preventing expression of the RA-responsive gene ripply3 within SHF progenitors.
2019-05-11 | GSE126747 | GEO