Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiles of fibroblasts from childhood cerebral adrenoleukodystrophy patients and healthy controls

ABSTRACT: Although not an affected cell type, skin fibroblasts from individuals with childhood cerebral adrenoleukodystrophy (CCALD), an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests. We report the gene expression profiles of fibroblasts from childhood cerebral adrenoleukodystrophy patients and healthy controls Primary dermal fibroblast cultures from 5 CC-ALD patients and 5 healthy controls were cultured in DMEM medium supplemented with 10% FBS at 37°C with 5% CO2 until confluence for RNA extraction. The overall goal was to identify genes that are differentially expressed between CCALD patients and healthy controls

ORGANISM(S): Homo sapiens

SUBMITTER: Joseph Hacia

PROVIDER: E-GEOD-34308 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis.

Wang Xiao-Ming XM Yik Wing Yan WY Zhang Peilin P Lu Wange W Dranchak Patricia K PK Shibata Darryl D Steinberg Steven J SJ Hacia Joseph G JG

Stem cell research & therapy 20121004 5

<h4>Introduction</h4>X-linked adrenoleukodystrophy (X-ALD) is a complex disorder with variable expressivity that affects the nervous, adrenocortical and male reproductive systems. Although ABCD1 mutations are known to provide the genetic basis for X-ALD, its pathogenesis is not fully elucidated. While elevated very long chain fatty acid (VLCFA) levels in blood and reduced VLCFA catabolic activity in cultured fibroblasts are biomarkers used to identify ABCD1 mutation carriers, the roles peroxisom ...[more]

PMID: 23036268

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Project description:X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms. How same mutation in the ABCD1 gene can lead to clinically very distinct phenotypes and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. We wonder whether epigenetics mechanisms could answer the lack of genotype-phenotype correlation. We employed Illumina state of the art technology to analyze the differential methylation of over 485,000 CpG sites throughout the entire human genome and used stringent statistical criteria to define differential methylation patterns between brains of cALD, cAMN and age-matched controls. We identified a common X-ALD methylation signature comprising the hypermethylation in genes harboring the trimethylated histone H3K27me3 mark in their promoters, the hypermethylation for genes driven the oligodendrocyte lineage, and the hypomethylation for immune-associated genes. We also examined the methylated differences between cALD and cAMN resulting with differential immune response pathways and concordance methylation levels with phenotype severity. The detected methylation differences correlated with transcriptional and translational consequences, as supported by Affymetrix expression arrays, quantitative PCR and WB changes. The reliability of these changes was further demonstrated by validating DNA methylation by an independent pyrosequencing assay. From these evidences, we propose the altered transcriptional programs in oligodendrocyte differentiation in X-ALD patients. These observations may provide new therapeutic epigenetic agents.

Dataset Information

Gene expression profiles of fibroblasts from childhood cerebral adrenoleukodystrophy patients and healthy controls

Publications

The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis.

Similar Datasets

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