Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic profile of three-dimensional tissue-engineered human skeletal muscle model of Pompe disease and recombinant protein therapy

ABSTRACT: Transcriptomic profile of three-dimensional tissue-engineered human skeletal muscle model of Pompe disease and recombinant protein therapy

PROVIDER: PRJNA667502 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12776587_1.fastq.gz	Fastqsanger.gz
	SRR12776587_2.fastq.gz	Fastqsanger.gz
	SRR12776588_1.fastq.gz	Fastqsanger.gz
	SRR12776588_2.fastq.gz	Fastqsanger.gz
	SRR12776589_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 20

Similar Datasets

Transcriptomic profile of three-dimensional tissue-engineered human skeletal muscle model of Pompe disease and recombinant protein therapy

Project description:Pompe disease (glycogen storage disease type II, or acid maltase deficiency) is an autosomal-recessive disorder of metabolism caused by mutations in the lysosomal hydrolase, acid alpha-glucosidase gene (GAA), resulting in progressive muscle atrophy. The current standard of care treatment, enzyme replacement therapy, consists of delivering recombinant human GAA (rhGAA) to reduce muscle glycogen and improve patient quality of life. With the aim of developing in vitro systems to study human disease and test therapies, we applied RNA sequencing to 3D tissue-engineered human skeletal muscle to compare healthy, (infantile onset) Pompe disease, and rhGAA-treated Pompe engineered tissues.

2020-10-06 | GSE159062 | GEO

Three-dimensional tissue-engineered human skeletal muscle model of Pompe disease.

Project description:In Pompe disease, the deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) causes skeletal and cardiac muscle weakness, respiratory failure, and premature death. While enzyme replacement therapy using recombinant human GAA (rhGAA) can significantly improve patient outcomes, detailed disease mechanisms and incomplete therapeutic effects require further studies. Here we report a three-dimensional primary human skeletal muscle ("myobundle") model of infantile-onset Pompe disease (IOPD) that recapitulates hallmark pathological features including reduced GAA enzyme activity, elevated glycogen content and lysosome abundance, and increased sensitivity of muscle contractile function to metabolic stress. In vitro treatment of IOPD myobundles with rhGAA or adeno-associated virus (AAV)-mediated hGAA expression yields increased GAA activity and robust glycogen clearance, but no improvements in stress-induced functional deficits. We also apply RNA sequencing analysis to the quadriceps of untreated and AAV-treated GAA-/- mice and wild-type controls to establish a Pompe disease-specific transcriptional signature and reveal novel disease pathways. The mouse-derived signature is enriched in the transcriptomic profile of IOPD vs. healthy myobundles and partially reversed by in vitro rhGAA treatment, further confirming the utility of the human myobundle model for studies of Pompe disease and therapy.

| S-EPMC8100136 | biostudies-literature

Three-dimensional tissue-engineered human skeletal muscle model of satellite cell quiescence

Project description:Three-dimensional tissue-engineered human skeletal muscle model of satellite cell quiescence

| PRJNA777926 | ENA

Transcriptomic profile of a skeletal muscle model of Pompe disease and recombinant protein therapy

Project description:Transcriptomic profile of a skeletal muscle model of Pompe disease and recombinant protein therapy

| PRJNA667499 | ENA

Three-dimensional tissue-engineered human skeletal muscle model of satellite cell quiescence

Project description:In vivo, satellite cells (SCs) are essential for skeletal muscle repair. However, in vitro investigation of SC function is challenged by isolation-induced SC activation, loss of the native quiescent state, and differentiation to myoblasts. This study applies tissue-engineered human skeletal muscle to track myoblast deactivation to 3D-SCs, which bear a quiescent phenotype, as well as examine melittin-induced injury response.

2021-11-11 | GSE188215 | GEO

Rescue of advanced Pompe disease in mice with hepatic expression of secretable acid α-glucosidase

Project description:Pompe disease is a neuromuscular disorder caused by mutations in the gene encoding for the lysosomal enzyme acid α-glucosidase (GAA). GAA converts lysosomal glycogen to glucose, and its deficiency leads to pathologic glycogen accumulation. Enzyme replacement therapy (ERT) is the only available treatment for Pompe disease at the moment with several shortcomings. We have shown that liver expression of secGAA has better therapeutic efficacy than non-engineered GAA after long-term treatment of four months old Gaa-/- mice with low vector doses. Based on those results, we have treated severely affected nine months old Gaa-/- mice with the AAV-secGAA vector and followed the animals for nine months thereafter. At the end of the study, AAV-treated Gaa-/- mice showed complete rescue of the Pompe phenotype. Transcriptomic profiling of skeletal muscle highlighted mitochondrial bioenergetics defects, supported by electron microscopy, western blotting and biochemical findings, which were partially corrected after AAV treatment. Together, these results provide insight into the reversibility of advanced Pompe disease in the Gaa-/- mouse model via liver gene transfer of secGAA.

2021-04-26 | GSE150935 | GEO

Transcriptome assessment of the Pompe (Gaa-/-) mouse cervical cord confirms widespread neuropathology.

Project description:The only FDA approved therapy for Pompe is directed at correcting skeletal and cardiac muscle pathology, however, clinical and animal model data show strong histological evidence for a neurological disease component. While neuronal cell death and neuroinflammation are prominent in many lysosomal disorders, these processes have not been evaluated in Pompe disease. There is also no information available regarding the impact of Pompe disease on the fundamental pathways associated with synaptic communication. We used microarrays to gain insight regarding pathogenetic signaling pathways that might contribute to neuropathology in Pompe (Gaa-/-) mice.

2016-10-11 | GSE82081 | GEO

GAA deficiency (Pompe Disease) in infantile-onset patients

Project description:Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.

2012-06-14 | GSE38680 | GEO

Pompe disease induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification

Project description:Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease. Total RNA were isolated from HESC, HF(Pompe disease), PomD-iPSC, HES-CMLC, and PomD-iPS-CMLC. The series included two HESC lines, two HF(Pompe disease) cell lines, four PomD-iPS cell lines, and HES-CMLC were differentiated from one HESC line(HESC2), PomD-iPS-CMLC were differentiated from 3 PomD-iPS cell lines(PomD-iPSC A10, PomD-iPSC A17, PomD-iPSC B03). Each condition was repeated twice and used HESC as control.

2011-02-17 | E-GEOD-27280 | biostudies-arrayexpress

GAA deficiency in Pompe disease is alleviated by exon inclusion in iPS cell-derived skeletal muscle cells

Project description:While there are many human skeletal muscle disorders, very few therapies have been developed. It has not been possible to generate large amounts of purified skeletal muscle cells from pluripotent stem cells, and to test therapies quantitatively. We therefore devised conditions for generating and expanding purified human myogenic progenitors from induced pluripotent stem (iPS) cells. The progenitors retained the capacity to differentiate into multinucleated myotubes and showed a normal karyotype throughout the expansion phase. We applied this method to Pompe disease, a metabolic myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). In a screen, we identified sequences that suppressed aberrant GAA exon 2 splicing caused by the frequent c.-32-13T>G (IVS1) GAA variant. Antisense oligonucleotides (AONs) that blocked these sequences promoted exon 2 inclusion in patient-derived myotubes. As this raised GAA enzymatic activity above the disease threshold, AON-mediated splicing correction may provide a treatment option for Pompe disease.

2017-04-11 | GSE75713 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data