RNA-seq analysis of Retinoic Acid and Non-treated Control hiPSCs
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE112695 | GEO | 2018/04/06
REPOSITORIES: GEO
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Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-cardiomyocytes) are promising sources for the regenerative therapy to treat heart failure. To realize this therapy, the engraftment potential of hiPSC-cardiomyocytes following the injection into the host heart should be improved. Here, we established the efficient method to analyze the cell cycle activity of hiPSC-cardiomyocytes using Fluorescence Ubiquitination-based Cell Cycle Indicator (FUCCI) system. High-throughput screening analysis using FUCCI-expressing hiPSC-cardiomyocytes identified a retinoic acid receptor (RAR) agonist, Am80, as an effective cell cycle activator in hiPSC-cardiomyocytes. The transplantation of hiPSC-cardiomyocytes treated by Am80 prior to the injection significantly enhanced the engraftment into the damaged mouse heart for 6 months. RNA sequencing analysis in Am80-treated iPSC-cardiomyocytes revealed that both RARA and RARB played important roles in the Am80-mediated cell cycle activation in hiPSC-cardiomyocytes. Collectively, this study highlights the effectiveness of FUCCI system to easily analyze the cell cycle status in hiPSC-cardiomyocytes and the cell cycle activation by Am80 is the possible strategy to increase the graft size following the cell transplantation into the damaged heart.
2023-07-12 | GSE176303 | GEO
Project description:RNA-seq analysis of Retinoic Acid and Non-treated Control hiPSCs
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Project description:Global expression profiling of osteogenic differeintiation with retinoic acid or without retinoic acid for two days from hiPSC
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Project description:Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. Using this method, we generated hiPSC-derived astrocyte populations (hiPSC-astrocytes) from 42 NPC lines (derived from 30 individuals) with an average of ~90% S100β-positive cells. Transcriptomic analysis demonstrated that the hiPSC-astrocytes are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our novel protocol is a reproducible, straightforward (single media) and rapid (<30 days) method to generate homogenous populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.
2017-08-18 | GSE97904 | GEO
Project description:Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and has a unique phenotype with characteristically extensive hypertrabeculation of the left ventricle, similar to the embryonic left ventricle, suggesting a developmental defect of the embryonic myocardium. However, studying this disease has been challenging due to the lack of an animal model that can faithfully recapitulate the clinical phenotype of LVNC. To address this, we show that patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) generated from a family with LVNC recapitulated a developmental defect consistent with the LVNC phenotype at the single-cell level. We then utilized hiPSC-CMs to show that increased transforming growth factor beta (TGFβ) signaling is one of the central mechanisms underlying the pathogenesis of LVNC. LVNC hiPSC-CMs demonstrated decreased proliferative capacity due to abnormal activation of TGFβ signaling. Exome sequencing demonstrated a mutation in TBX20, which regulates TGFβ signaling, contributing to the LVNC phenotype. Our results demonstrate that hiPSC-CMs are a useful tool for the exploration of novel mechanisms underlying poorly understood cardiomyopathies such as LVNC. Here we provide the first evidence of activation of TGF signaling as playing a role in the pathogenesis of LVNC.
2016-07-13 | GSE63161 | GEO
Project description:The retinoic acid (RA) signaling pathway is essential for cardiac development; however, cardiomyocytes, the main cell type of the heart, are considered to be unresposive to RA signaling. The goal of this study was to examine the effects of all-trans RA (atRA) treatment on cardiomyocytes isolated from E18.5 mouse embryos. We found that cardiomyocytes, contrary to previous findings, are indeed repsonsive to RA signaling and that many genes involved in cardiac developmental and repair processes were significantly deregulated upon atRA trearment. These findings have important implications for the heart development and regeneration fields.
2021-04-01 | GSE161429 | GEO
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:We are presenting the application of toxicogenomics in the evaluation of the toxic effects of retinoic acid and one of its isoforms the 9-cis retinoic acid. The main goal is to distinguish the pattern of action of the both chemical compounds and their action in an extended exposure. The results suggest a different pattern within the days and the chemicals. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of retinoic acid compounds studied.
2015-12-31 | GSE41335 | GEO
Project description:About one-third of oestrogen receptor alpha- positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen. Peptide and protein identification data set 1: Peptide identification from the MALDI-TOF/TOF data was carried out using the Paragon algorithm in the ProteinPilot 2.0 software package (Applied Biosystems) 46. Default settings for a 4800 instrument were used (i.e., no manual settings for mass tolerance was given). The following parameters were selected in the analysis method: iTRAQ 4plex peptide labelled as sample type, MMTS as alkylating agent of cysteine, trypsin as digesting enzyme, 4800 as instrument, gel based ID and Urea denaturation as special factors, biological modifications as ID focus, and thorough ID as search effort. Peptide identification from the Q-TOF data was carried out using the Spectrum Mill Protein Identification software (Agilent). Data was extracted between MH+ 600 and 4000 Da (Agilent's definition). Scans with the same precursor m/z 90 sec, 0.05 m/z matching with a minimum of 20 peaks in MS2 were merged. Peptide and protein identification data set 2: Proteome discoverer 1.3 with sequest-percolator was used for protein identification. Precursor mass tolerance was set to 10 ppm and for fragments 0.8 Da and 0.02 Da were used for detection in the linear iontrap and the orbitrap, respectively. Oxidized methionine and phosphorylation on S,T and Y was set as dynamic modifications, and carbamidomethylation, N-terminal 8plex iTRAQ, and lysyl 8plex iTRAQ as fixed modifications. Spectra were matched to ensembl 68 limited to human protein sequences, and results were filtered to 1% FDR.
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