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Study of the signaling modulated by HDAC4 in skeletal muscle in ALS

ABSTRACT: Study of the signaling modulated by HDAC4 in skeletal muscle in ALS

PROVIDER: PRJNA498450 | ENA |

REPOSITORIES: ENA

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Study of the signaling modulated by HDAC4 in skeletal muscle in ALS

Project description:BACKGROUND: Histone deacetylase 4 (HDAC4) has been proposed as a target for the treatment of Amyotrophic Lateral Sclerosis (ALS) because it mediates nerve-skeletal muscle interaction and since its expression in skeletal muscle correlates with the severity of the disease. However, our recent studies on the skeletal muscle response upon long-term denervation highlighted the importance of HDAC4 in maintaining muscle integrity. METHODS: To fully identify the yet uncharacterized HDAC4 functions in ALS, we genetically deleted HDAC4 in skeletal muscles of a mouse model of ALS. Body weight, skeletal muscle, innervation and spinal cord were analyzed over time by morphological and molecular analyses. A transcriptome analysis was also performed to delineate the signaling modulated by HDAC4 in skeletal muscle of a mouse model of ALS. FINDINGS: HDAC4 deletion in skeletal muscle caused earlier ALS onset, characterized by body weight loss, muscle denervation and atrophy, and compromised muscle performance in ALS mice, although the main catabolic pathways were not activated. A transcriptome analysis identified the gene networks modulated by HDAC4 in ALS, revealing UCP1 as a top regulator that may be implicated in worsening ALS features. INTERPRETATION: HDAC4 plays an important role in preserving innervations and skeletal muscle in ALS, likely by modulating the UCP1 gene network. Our study highlights a possible risk in considering HDAC inhibitors for the treatment of ALS.

2019-01-31 | GSE121789 | GEO

Samples from mouse skeletal muscle

Project description:samples from mouse Skeletal Muscle, analysis different expression profiling<br>HDAC4：Sciatic nerve transection model was prepared after injection of HDAC4-shRNA lentivirus into the tibialis anterior muscle of mice. 14 days later, tibialis anterior muscle was obtained. DenSciatic nerve transection model was prepared after injection of empty vector virus into the tibialis anterior muscle of mice. 14 days later, tibialis anterior muscle was obtained. N: The empty vector virus was injected into muscles from the sham group. 14 days later, tibialis anterior muscle was obtained.

2021-05-10 | E-MTAB-10072 | biostudies-arrayexpress

Hdac4 regulates proliferation of neural crest-derived osteoblasts during murine craniofacial development

Project description:Craniofacial development involves regulation of a compendium of transcription factors, signaling molecules and epigenetic regulators. Histone deacetylases (HDACs) are involved in the regulation of cell proliferation, differentiation and homeostasis across a wide range of tissues, such as brain, cardiovascular system, muscular system, and skeletal system. However, functional role of Hdac4 during craniofacial development is still unclear. In this study, we investigated the effects of Hdac4 knockout in craniofacial skeletal development by conditionally disrupting the Hdac4 gene in cranial neural crest cells (CNCCs) using Cre-mediated recombination. Mice deficient in Hdac4 in CNCCs-derived osteoblasts demonstrated a dramatic decrease in bone formation in frontal bone. In vitro pre-osteoblasts (MC3T3-E1 cells) lacking Hdac4 exhibited reduced proliferation activity in association with dysregulation of cell cycle-related genes. These findings suggest that Hdac4 acts partially as a regulator of craniofacial skeletal development by positively regulating proliferation of CNCCs-derived osteoblasts.

2022-03-09 | GSE186707 | GEO

Gene expression analysis of ALS skeletal muscle

Project description:Objective: to focus on the molecular mechanisms involved in the ALS related atrophy process that leads to selective wasting muscles . Design: gene expression profiling and real time PCR were performed on muscle biopsies

2013-02-28 | E-GEOD-41414 | biostudies-arrayexpress

Transcriptome analysis of satellite cells with a genetic deletion of HDAC4 to identify the gene modulated by HDAC4

Project description:Transcriptome analysis of satellite cells with a genetic deletion of HDAC4 to identify the gene modulated by HDAC4

| PRJNA416903 | ENA

Transcriptome analysis of satellite cells with a genetic deletion of HDAC4 to identify the gene modulated by HDAC4

Project description:NGS technology was used for high-throughput profiling of the transcriptome by comparing satellite cells lacking or not HDAC4.

2018-02-28 | GSE106445 | GEO

Gene expression analysis of ALS skeletal muscle

Project description:Objective: to focus on the molecular mechanisms involved in the ALS related atrophy process that leads to selective wasting muscles .

2013-02-28 | GSE41414 | GEO

Hdac4 interactome in Huntington's Disease

Project description:Hdac4 has been found to modulate symptoms in Huntington's Disease (HD) mouse models through an uknown mechanism unrelated to any enzymatic activity. We investigated the protein-protein interactions to gain insight into the role of Hdac4 in HD.

2019-05-01 | PXD011845 | Pride

Differentially modulated transcriptomes of mouse skeletal muscle (gastrocnemius) during postnatal development

Project description:Differentially modulated transcriptomes of mouse skeletal muscle (gastrocnemius) during postnatal development

| PRJNA427136 | ENA

Transcription profiling of skeletal muscle from amyotrophic lateral sclerosis sod1(G86R) axotomized mice and control mice to monitor denervation-dependent gene expression in an Amyotrophic lateral sclerosis (ALS) mouse model

Project description:Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular disorder characterized by the selective degeneration of upper and lower motor neurons, progressive muscle wasting and paralysis. To define the full set of alterations in gene expression in skeletal muscle during the course of the disease, we performed high-density oligonucleotide microarray analysis of gene expression in hind limb skeletal muscles of sod1(G86R) mice, one of the existing transgenic models of ALS. To monitor denervation-dependent gene expression, we determined the effects of short-term acute denervation on the muscle transcriptome after sciatic nerve axotomy.

2008-01-05 | E-TABM-195 | biostudies-arrayexpress

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