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Transcriptomic profiles of skin fibroblasts from patients affected by schizophrenia and controls

ABSTRACT: Whole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders. A microarray expression study was conducted comparing transcriptomic profiles of skin fibroblasts from SCZ patients and controls. Fibroblasts can be more advantageous to discover mental disorder aetiological mechanisms since they seem more similar to neurons and less affected by the environmental confounders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62333 | GEO | 2015/02/17

SECONDARY ACCESSION(S): PRJNA263840

REPOSITORIES: GEO

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Transcriptomic profiles of skin fibroblasts from patients affected by schizophrenia and controls

Project description:Whole-genome expression studies in peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insights into the molecular basis of the disorder and innovative biomarkers that may be of great usefulness in the clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful to investigate molecular alterations in psychiatric disorders. A microarray expression study was conducted comparing transcriptomic profiles of skin fibroblasts from SCZ patients and controls. Fibroblasts can be more advantageous to discover mental disorder aetiological mechanisms since they seem more similar to neurons and less affected by the environmental confounders. Transcriptomic profiles of human skin fibroblasts obtained from 20 schizophrenia patients were compared to 20 controls

2015-02-17 | E-GEOD-62333 | biostudies-arrayexpress

A human single cell atlas of the substantia nigra reveals novel cell specific pathways associated with the genetic risk of Parkinson’s disease and neuropsychiatric disorders

Project description:We describe the first human single-nuclei transcriptomic atlas for substantia nigra (SN), generated by sequencing ~ 17,000 nuclei from matched cortical and SN samples. We show that common genetic risk for Parkinson’s disease (PD) is associated with dopaminergic neuron (DaN)-specific gene expression including mitochondrial functioning, protein folding and ubiquitination pathways. We also identified a distinct cell-type association between PD risk and oligodendrocyte-specific expression implicating metabolic and gene expression regulation networks. Beyond PD, we find SN DaNs and GABAergic neurons to be associated with different neuropsychiatric disorders, particularly schizophrenia (SCZ) and bipolar disorder (BP). We identified distinct cortex/SN associations with SCZ genetic risk for both excitatory (synaptic functioning) and dopaminergic neurons (mitochondrial functioning and synaptic signalling). Conditional analyses shows that independent sets of loci associate distinct neuropsychiatric disorders with the same neuronal types. This atlas guides our aetiological understanding by associating SN cell-type expression profiles with specific disease risk.

2020-01-07 | GSE140231 | GEO

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

2012-03-01 | GSE34308 | GEO

Gene expression profiles of fibroblasts and fibroblast-reprogrammed induced pluripotent stem cells (iPSCs) from childhood cerebral adrenoleukodystrophy patients and healthy controls

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Gene expression profiles of hepatocyte-like cells derived from induced pluripotent stem cells (iPSCs) from donors with the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD) and healthy controls

Project description:Skin fibroblasts from individuals with PBD-ZSD, a rare autosomal recessive disorder caused by peroxisome assembly defects, show defects in lipid metabolism that provide the basis for clinical diagnostic tests, but are not among the cell types most affected by disease. To explore phenotypes of more clinically relevant cell types, skin fibroblasts from PBD-ZSD patients and healthy controls were reprogrammed into iPS cells with all the hallmark properties of pluripotency. Subsequently, iPSCs were differentiated into ASGPR-positive hepatocyte-like cells that were subject to flow cytometry and subject to gene expression profiling. We report the gene expression profiles of hepatocyte-like cells derived from iPSCs that were themselves derived from skin fibroblasts from PBD-ZSD patient donors and healthy controls.

2015-05-21 | GSE69066 | GEO

Characterization and Plasticity of the Metabolome in Peripheral Cells in Bipolar I Disorder

Project description:Patients with Bipolar I Disorder (BPI) and matched non-affected controls were recruited. Males and females from all races and ethnicities between the ages of 19-65 participated in the research. Skin biopsies were obtained and fibroblasts were isolated from each of these biopsies. A total of 1 x 〖10〗^7 fibroblasts cells were used for metabolomics. Cell pellets were flash frozen in liquid nitrogen and shipped on dry ice to the NIH Eastern Regional Comprehensive Metabolomic Resource Core at RTI International in North Carolina. Metabolomics will be determined using a broad spectrum metabolomics protocol by RTI

2016-03-05 | ST000361 | MetabolomicsWorkbench

Transcriptomic signatures of risk genes implicated in psychiatric disorders during neuronal differentiation

Project description:Susceptibility genes for Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), monogenetic disorders with intellectual disabilities (ID) or schizophrenia (SCZ) converge on processes related to neuronal function and differentiation. Furthermore, ASD risk genes are enriched for FMRP (Fragile X Mental Retardation Protein) targets and for genes implicated in ID. In addition, a significant co-heritability was observed between ASD and SCZ. The genetic overlap between ASD, FXS, ID and SCZ together with the symptomatic differences gives rise to the question if pathomechanisms impair the same or different regulatory patterns activated during neuronal differentiation (ND). To test this idea, we performed transcriptome analysis of in-vitro differentiation of the neuroblastoma cell line model SH-SY5Y and identified genes that were differentially expressed, dynamically regulated, and coordinately expressed. The identified genetic modules activated during ND are enriched for genetic risk factors for these four disorders. Although risk genes for the disorders significantly overlap, we observed disorder specific enrichments: ASD or FXS implicated genes were likely to be positive regulators of ND whereas ID implicated genes were related to negative regulation. ASD and SCZ genes were specifically enriched among cholesterol and fatty acid associated modules. ID genes were overrepresented among cell cycle modules. In addition, we show that ASD genes are likely to be hub genes. We hypothesize that knowledge about genetic variants of an individual combined with network and pathway context of the related genes will allow differentiating between psychiatric disorders. 21 samples, consisting of 3 replicates harvested at 7 different time-points of RA+BDNF-induced neuronal differentiation

2016-06-01 | E-GEOD-69838 | biostudies-arrayexpress

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

Project description: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

2012-03-01 | E-GEOD-34308 | biostudies-arrayexpress

Gene expression profiles of fibroblasts and fibroblast-reprogrammed induced pluripotent stem cells (iPSCs) from childhood cerebral adrenoleukodystrophy patients and healthy controls

Project description:Although not an affected cell type, skin fibroblasts from individuals with CC-ALD, 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. Skin fibroblasts from CC-ALD patients can be reprogrammed into iPS cells with all the hallmark properties of pluripotency. The iPS cell phenotypes may reflect the tissue-specificity of the lipid metabolic defects found in CC-ALD patients. We report the gene expression profiles of fibroblasts and fibroblast-reprogrammed iPSCs from childhood cerebral adrenoleukodystrophy patients and healthy controls Dermal fibroblast cultures from 2 CCALD patients and 3 healthy controls were reprogrammed into iPSCs by transfection with retroviruses desinged to express the human OCT4, SOX2, KLF4 and c-MYC cDNA. Fibroblasts and iPSCs were cultured in 1:1 ratio of DMEM/F12 medium supplemented with 20% KSR 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.

2012-03-01 | E-GEOD-34309 | biostudies-arrayexpress

Expression profiling of skin fibroblast and iPSC from Werner Syndrome

Project description:The premature aging disorder Werner Syndrome (WS) is characterized by early onset of aging phenotypes resembling natural aging. In most WS patients there are mutations in the DNA helicase WRN, an enzyme important in maintaining genome stability and telomere replication. Interestingly, its clinical manifestations reflect a severe degree of deterioration for connective tissue, whereas the central nervous system is less affected. We suggest that the varied vulnerability to aging is regulated by an unknown mechanism that protects specific lineages of stem cells from premature senescence. To address this problem, we reprogrammed patient skin fibroblasts to induced pluripotent stem cells (iPSC). The expression profile for the differentiated normal and WS fibroblasts and undifferentiated iPSC were compared. A distinct expression profile was found between normal and WS fibroblasts, however, few changes of gene expression were found in iPSC. Our findings suggest an erasure of aging phenotype associated with WS in reprogrammed iPSC. Human normal and WS skin fibroblasts were reprogrammed to induced pluripotent stem cells (iPSC). These samples, before and after reprogramming, were analyzed for the change of gene expression profile.

2013-07-11 | E-GEOD-48761 | biostudies-arrayexpress

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