Transcriptomic analysis of day 1 (D1) differentiating WT and HDAC11-deficient mouse myoblasts
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE147423 | GEO | 2020/07/10
REPOSITORIES: GEO
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Project description:Transcriptomic analysis of day 1 (D1) differentiating WT and HDAC11-deficient mouse myoblasts
| PRJNA614530 | ENA
Project description:HDAC11 regulates IL-10 expression and overexpression of HDAC11 in antigen presenting cells (APCs) leads to a pro-inflammatory phenotype. Conversely, loss of HDAC11 leads to upregulation of IL-10 and immune tolerance. HDAC11 overexpression is also associated with inflammatory diseases including multiple sclerosis. Hence we wished to determine the inflammatory mediators regulated by HDAC11. We used microarray to determine gene expression profile of macrophages from WT and HDAC11 knockout mice. Thioglycollate induced-peritoneal macrophages obtained from WT and HDAC11 knockout mice were used for total RNA extraction to determine changes in gene expression levels in macrophages from WT and HDAC11 knockout mice.
2014-03-31 | E-GEOD-56366 | biostudies-arrayexpress
Project description:HDAC11 regulates IL-10 expression and overexpression of HDAC11 in antigen presenting cells (APCs) leads to a pro-inflammatory phenotype. Conversely, loss of HDAC11 leads to upregulation of IL-10 and immune tolerance. HDAC11 overexpression is also associated with inflammatory diseases including multiple sclerosis. Hence we wished to determine the inflammatory mediators regulated by HDAC11. We used microarray to determine gene expression profile of macrophages from WT and HDAC11 knockout mice.
2014-03-31 | GSE56366 | GEO
Project description:Bone morphogenetic proteins (BMPs) trigger as cell-extrinsic signals the differentiation of neural crest progenitor cells to the sympathoadrenal cell lineage. Human neuroblastoma derives from aberrant neural crest progenitor cells. We here show that histone deacetylase 11 (HDAC11), the most recently identified family member with, as yet, largely unknown function, is recruited to the BMP4 gene promoter and represses its transcription in neuroblastoma. Both HDAC11 depletion and enzymatic inhibition revert the epigenetic silencing of BMP4, thereby blocking a critical oncogenic function of HDAC11. Activated BMP4 signaling through targeting of HDAC11 induces a transcriptional profile predictive of favorable prognosis for patients when expressed in the tumors, indicating that the HDAC11-BMP4 axis plays a critical role for neuroblastoma biology. Furthermore, pathway activation causes MYCN proto-oncogene repression on a molecular level and anti-proliferative effects in functional assays in neuroblastoma cell lines and primary sphere cultures as well as strongly inhibiting tumor formation and growth of subcutaneous neuroblastoma xenografts in mice. For high-risk neuroblastoma, with cure rates below 30% using current treatment strategies, our work suggests a novel targeted therapeutic approach that would reactivate the developmental pathway inducing normal differentiation of neural crest progenitor cells.
2014-12-31 | GSE20399 | GEO
Project description:In this experiment we have analyzed the effect of TGFbeta-1 incubation (3h of incubation time) on the gene expression profiles of human primary cultured skeletal muscle cells, both in growing myoblasts or in differentiated muscle fibres (after 10-days of differentiation), obtained from skeletal muscle biopsies from a 2-months old healthy donor and a 5-years old DMD (Duchenne Muscular Dystrophy) patient. All human skeletal muscle biopsies were obtained by surgery from calf muscles with informed consent and approval of the Human Use Committee of Vall d'Hebron University Hospital (Barcelona, Spain). Human myoblasts were cultured on 6 cm plates until reached 70-80% of confluence and then, were incubated for 3h in the presence or in absence of TGF-?1 (2.5 ng/ml). Skeletal muscle fibres were obtained by growing human myoblasts on 6 cm plates until reached 70-80% of confluence and then, cells were induced to differentiate by deprivation of growth factors in the culture medium. After 10 days of differentiation, skeletal muscle fibers were incubated for 3h in the presence or in absence of TGFbeta-1 (2.5 ng/ml). In all cases, immediately after TGFbeta-1 treatment the RNA was extracted and used for Affymetrix microarrays analysis using the U133 2.0 microarray genechips.
2016-08-07 | E-MEXP-2937 | biostudies-arrayexpress
Project description:We tested the hypothesis that ectopic expression of the MyoD-dependent gene program in differentiating myoblasts and myotubes compromises the integrity of the plasma membrane/sarcolemma by using a doxycycline-inducible system to overexpress MyoD in C2C12 myoblasts during differentiation. The overarching goals of this analysis pipeline were to (a) determine changes in transcriptional profiles upon sustained overexpression of MyoD during and upon differentiation; and, (b) utilize these profiles to identify potential drivers of sarcolemmal fragility that exacerbate myofiber damage and loss in dystrophic muscle. We used microarrays to generate information about transcriptional profiles in differentiating myoblasts and myotubes overexpressing the myogenic transcription factor myoblast determination protein 1 (MyoD1).
2022-05-03 | GSE168703 | GEO
Project description:The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas significantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identified a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicates a significant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target.
2017-02-16 | GSE77080 | GEO
Project description:Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into nucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Ribonucleoprotein immunoprecipitation (RIP) analysis showed that MYF5 bound a subset of myoblast mRNAs; prominent among them was Ccnd1 mRNA, which encodes the key cell cycle regulator CCND1 (Cyclin D1). Biotin-RNA pulldown, UV-crosslinking, and gel shift experiments indicated that MYF5 was capable of binding the 3' untranslated region (UTR) and the coding region (CR) of Ccnd1 mRNA. MYF5 silencing in proliferating growing myoblasts revealed that and MYF5 promoted CCND1 translation, and it also modestly increased transcription of Ccnd1 mRNA. Importantly, silencing MYF5 reduced myoblast growth as well as differentiation of myoblasts into myotubes, while overexpressing MYF5 in C2C12 cells upregulated CCND1 expression. We propose that MYF5 enhances early myogenesis in part by coordinately elevating Ccnd1 transcription and Ccnd1 mRNA translation. Four replicates were utilized from either Control (IgG) or MYF5-immunoprecipitated RNA samples from C2C12 cells growing in either growth medium (GM) or differentiation medium (DM) for a total of sixteen samples.
2016-08-08 | E-GEOD-73704 | biostudies-arrayexpress
Project description:GDF8 (myostatin) is a unique cytokine strongly affecting the skeletal muscle phenotype in human and animals. The aim of the present study was to elucidate the molecular mechanism of myostatin influence on the differentiation of mouse C2C12 myoblasts, using the global-transcriptome analysis with the DNA microarray technique. Treatment with exogenous GDF8 strongly affected the growth and development of C2C12 mouse myoblasts. This was manifested by the inhibition of proliferation and differentiation as well as the impairment of cell fusion. DNA microarray analysis revealed 778 genes regulated by GDF8 in differentiating myoblasts (543 down-regulated and 235 up-regulated). Ontological analysis revealed their involvement in 17 types of biological processes, 10 types of molecular functions and 68 different signaling pathways. The effect of GDF8 was mainly mediated by the disruption of the cell cycle, calcium and insulin signaling pathways and expression of cytoskeletal and muscle specific proteins. The identified key-genes that could play a role as GDF8 targets in differentiating myoblasts are: Mef2, Hgf, Ilb1, Itgb1, Edn1, Ppargc1a. After scanning of hybridized microarrays, quantitation of slide images was performed using Feature Extraction Software (Agilent) using default parameters. The raw data were normalized by Loess normalization method, and then the normalized raw data was exported to GeneSpring GX 11.0.5 (Agilent, Santa Clara, CA). For identification of genes significantly altered in cell compared with the control normal gene set, total detected entities were filtered by flags (present, marginal) to remove very low signal entities and to select reproducible signal values of entities among the replicated experiments, respectively. In statistical analysis, separated for experiment with myoblasts treated with GDF8 ([C2C12]-[GDF8]1-4) was used t-test unpaired (p < 0.05) and fold change over 1.6. Analysis of GO and signaling pathway was carried out using GeneSpring GX 12 (Agilent), KEGG and PANTHER Classification System (http://www.pantherdb.org/). In the analysis of signaling pathways using Panther, a total of 68 cellular pathways were identified.
2014-07-23 | E-GEOD-59674 | biostudies-arrayexpress
Project description:Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into nucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Ribonucleoprotein immunoprecipitation (RIP) analysis showed that MYF5 bound a subset of myoblast mRNAs; prominent among them was Ccnd1 mRNA, which encodes the key cell cycle regulator CCND1 (Cyclin D1). Biotin-RNA pulldown, UV-crosslinking, and gel shift experiments indicated that MYF5 was capable of binding the 3' untranslated region (UTR) and the coding region (CR) of Ccnd1 mRNA. MYF5 silencing in proliferating growing myoblasts revealed that and MYF5 promoted CCND1 translation, and it also modestly increased transcription of Ccnd1 mRNA. Importantly, silencing MYF5 reduced myoblast growth as well as differentiation of myoblasts into myotubes, while overexpressing MYF5 in C2C12 cells upregulated CCND1 expression. We propose that MYF5 enhances early myogenesis in part by coordinately elevating Ccnd1 transcription and Ccnd1 mRNA translation.
2016-08-08 | GSE73704 | GEO