Prolonged FOS Activity Disrupts A Global Myogenic Transcriptional Program By Altering 3D Chromatin Architecture in Primary Muscle Progenitor Cells
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ABSTRACT:
PROVIDER: PRJNA699764 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13639801.fastq.gz | Fastqsanger.gz | |||
| SRR13639802.fastq.gz | Fastqsanger.gz | |||
| SRR13639803.fastq.gz | Fastqsanger.gz | |||
| SRR13639804.fastq.gz | Fastqsanger.gz | |||
| SRR13639805.fastq.gz | Fastqsanger.gz |
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Project description:Background Quiescent (non-dividing) muscle satellite cells (SCs) transition into proliferating progenitor cells that differentiate to repair skeletal muscle after injury. Recently, the AP-1 family member, FOS, was found to be rapidly and transiently induced in SCs in response to muscle damage, and its activity is required for effective SC activation and muscle repair. However, why FOS is rapidly down-regulated before SCs enter the cell cycle as progenitor cells remains unclear. In addition, whether boosting FOS expression in primary cycling muscle progenitor cells can enhance their myogenic properties needs to be evaluated. Methods In this study, we established a lentiviral, doxycycline-inducible system to explore the molecular and functional consequences of continued FOS expression in SC-derived, cycling muscle progenitor cells ex vivo. Specifically, we performed cell growth and EdU incorporation assays to measure cellular proliferation; myotube formation assays to evaluate terminal differentiation potential; and RNA-Sequencing (RNA-Seq) in conjunction with high-throughput chromosome conformation capture (Hi-C) to uncover changes in gene expression and long-range chromatin interactions. Results Persistent FOS activity in cycling muscle progenitor cells modestly enhances progenitor cell proliferation, but severely antagonizes their ability to differentiate and form myotubes. Genome-wide RNA-Seq analysis revealed that ectopic FOS activity in cycling muscle progenitor cells suppresses a global pro-myogenic gene expression program, while activating a stress-induced Mitogen-Activated Protein Kinase (MAPK) transcriptional signature. Importantly, we found various chromosomal re-organization events in A/B compartments, TADs, and long-range genomic loops near FOS-regulated differentially expressed genes in cycling muscle progenitor cells ectopically expressing FOS. Conclusions Altogether, our results suggest that elevated FOS activity in proliferating muscle progenitor cells perturbs cellular differentiation by altering the 3-dimensional (3D) chromosome organization near critical pro-myogenic genes. This work highlights the crucial importance of tightly controlling FOS expression in the muscle lineage, and raises the possibility that in states of chronic stress or disease, persistent FOS activity in muscle stem and/or progenitor cells may actually disrupt the muscle forming process.
2022-08-15 | GSE166241 | GEO
Project description:Loss of the Nuclear Envelope Protein LAP1B Disrupts Myogenic Differentiation of Patient-Derived Fibroblasts
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Project description:Acinetobacter baumannii is a highly pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. Our results suggest that bacterial infection interacts with host tryptophan metabolism and the transcription factor FOS.
2024-08-05 | PXD053768 | Pride
Project description:Analysis of the transcriptome of zebrafish mononuclear myogenic cells (zMNCs) during myogenic differentiation. The main goal is to identify the similarities of zMNC myogenic differentiation with that of mammalian myoblast differentiation. Critical time points were used to identify a switch from the activity of cell proliferation genes to myogenic structural genes. 15-20 adult zebrafish dorsal skeletal muscles were isolated at each of 6 distinct time points (day 0, day 1, day 4, day 7, day 10, day 14) in replicates.
2010-04-07 | E-GEOD-19754 | biostudies-arrayexpress
Project description:Lamina-associated polypeptide 1 (LAP1) is a ubiquitously expressed inner nuclear membrane protein encoded by TOR1AIP1, and present as two isoforms in humans, LAP1B and LAP1C. While loss of both isoforms results in a multisystemic progeroid-like syndrome, specific loss of LAP1B causes muscular dystrophy and cardiomyopathy, suggesting that LAP1B has a critical role in striated muscle. To gain more insight into the molecular pathophysiology underlying muscular dystrophy caused by LAP1B, we established a patient-derived fibroblast line transdifferentiated into myogenic cells with inducible MyoD expression. Compared to controls, we observed strikingly reduced myogenic differentiation and fusion potentials. Similar defects were observed in C2C12 myoblasts carrying loss-of-function LAP1A/B mutations. Using RNA sequencing, we showed that despite MyoD overexpression and efficient cell cycle exit, transcriptional reprogramming of LAP1B-deficient cells into the myogenic lineage was impaired with delayed activation of myogenin and muscle-specific downstream genes. Gene set enrichment analysis suggested dysregulation of protein metabolism, extracellular matrix and chromosome organization. Finally, we found that LAP1B-deficient cells exhibit nuclear deformations such as increased micronuclei and altered morphometric parameters. This study reports the phenotypic and transcriptomic changes during myoconversion of patient-derived fibroblasts and provides a useful resource to gain new insights into the mechanisms implicated in LAP1B-associated nuclear envelopathies.
2022-10-02 | GSE214495 | GEO
Project description:Analysis of the transcriptome of zebrafish mononuclear myogenic cells (zMNCs) during myogenic differentiation. The main goal is to identify the similarities of zMNC myogenic differentiation with that of mammalian myoblast differentiation. Critical time points were used to identify a switch from the activity of cell proliferation genes to myogenic structural genes.
2010-03-30 | GSE19754 | GEO
Project description:c-Fos, a member of the stress-activated Activator Protein 1 (AP-1) transcription factor family, is expressed in human hepatocellular cancer (HCC). Using genetically engineered mouse models (GEMMs) we show that hepatocyte-specific expression of c-Fos leads to a proliferative, de-differentiated phenotype, whereas hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced liver cancer. Furthermore, c-Fos-expressing livers resemble human HCCs based on expression profiles. In the present RNA seq, we intend to analyze the transcriptomic profile of livers at 2 and 4 mo hepatocyte-specific c-Fos expression compared to the corresponding age-matched control mice. Moreover, we analyzed livers of mice with hepatocyte-specific deletion c-Fos at 48h after DEN treatment compared to identically treated control mice.
2017-03-23 | GSE81079 | GEO
Project description:Rhabdomyosarcoma (RMS) is a frequent non-epithelial tumor of soft tissue that originates from a myogenic differentiation defect. Expression of SNAIL transcription factor is elevated in the alveolar subtype of RMS, characterized by a low myogenic differentiation status and high aggressiveness. SNAIL affects RMS metastasis by reorganization of actin cytoskeleton, regulation of ezrin expression and chemotaxis to HGF and SDF-1. The differentiation of human RMS diminishes SNAIL level. SNAIL silencing completely abolishes the growth of human RMS xenotransplants. SNAIL inhibits myogenic differentiation of RMS by binding to the MYF5 promoter, suppressing its expression, displacing MYOD from canonical to alternative E-box sequences and regulating myomiRs expression. SNAIL silencing allows the re-expression of MYF5 and canonical MYOD binding, promoting RMS cell myogenic differentiation. These novel results open potential avenues for the development of innovative therapeutic strategies based on SNAIL silencing.
2020-07-14 | PXD006711 | Pride
Project description:A shotgun microarray-based approach was used to identify candidate genes encoding the FOS utilization pathway in L. paracasei 1195. Differential expression profiles between cells grown on FOS and glucose provided a basis for identifying genes specifically induced by FOS. In addition, transcriptional analysis of cells grown on FOS or FOS + glucose allowed us to investigate the effect of catabolite repression on the expression of the FOS-induced genes. For sugar induction experiment (FOS vs. glucose; FOS vs. fructose), L. paracasei were grown in modified MRS (mMRS) basal medium to a final OD625 nm of ca. 0.3, at which point all of the residual sugars in the medium were consumed (based on HPLC analysis of the supernatants). The culture was then divided into equal portions, where FOS or glucose was added to a 1% final concentration. Cells were collected for total RNA isolation after 30 min (OD625 nm ca. 0.3 â 0.4). For glucose repression experiment (FOS vs. FOS + glucose), cells were grown in mMRS supplemented with 2% FOS to an OD625 nm 0.6. The culture was split into equal portions, and glucose was added to one of the portions at a 2% final concentration. Both cultures were grown for another 60 min (OD625 nm ca. 1.0) before harvested for total RNA isolation. Both experiments were performed in independent replicates (two biological replicates per experiment) with incubation at 37 degree celsius in ambient atmosphere.
2010-06-30 | E-GEOD-5890 | biostudies-arrayexpress
Project description:Proto-oncogene c-Fos is a leucine-zipper containing transcription factor which has a DNA binding domain and a transactivation domain. Fos dimerizes with another transcription factor Jun to form AP1 transcription factor. The AP-1 complex has been implicated in transformation and progression of cancer. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Map binding sites of transcription factor Fos in the genome of K562 cells. The K562 input data has been deposited in GEO as GSM325934.
2009-12-31 | E-GEOD-19546 | biostudies-arrayexpress