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Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.

ABSTRACT: Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia.

SUBMITTER: Etemadikhah M

PROVIDER: S-EPMC6971273 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.

Etemadikhah Mitra M Niazi Adnan A Wetterberg Lennart L Feuk Lars L

Scientific reports 20200120 1

Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, t ...[more]

PMID: 31959813

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Project description:Dietary threonine (Thr) deficiency increases hepatic triglyceride accumulation in Pekin ducks, which results in fatty liver disease and impairs hepatic function. However, the underlying molecular mechanisms altered by dietary Thr deficiency are still unknown. To identify the underlying molecular changes, 180 one-day-old ducklings were divided into three groups, including Thr deficiency group (Thr-D), Thr sufficiency group (Thr-S), and pair-fed group (Pair-F) that was fed with a Thr-sufficient diet but with reduced daily feed intake. The results showed that feed intake was similar between Thr-D and Pair-F groups, but weight gain rate and final body weight in the Thr-D group were lower than those in the Pair-F group. Feed intake, weight gain, and body weight in Thr-D and Pair-F groups were lower than those in the Thr-S group. The Thr-D diet reduced abdominal fat percentage but increased hepatic triglyceride content when compared with that of the Thr-S and Pair-F groups. The Pair-F reduced hepatic levels of C15:0, C17:0, C18:0, C20:0, C20:4n6, and C22:0 and also reduced total fatty acid, saturated fatty acid, and unsaturated fatty acid content when compared with those of the Thr-D and Thr-S groups. The Thr-D diet increased hepatic content of C6:0, C17:1, C18:3n6, C20:0, C20:1n9, and C22:2, as well as reduced the content of C18:2n6t and C23:0 when compared with those of the Thr-S group. Transcriptome analysis in the liver indicated that the Thr-D diet upregulated genes related to fatty acid and triglyceride synthesis and downregulated genes related to fatty acid oxidation and triglyceride transport. Gene ontology analysis showed that more genes related to lipid metabolism processes and molecular function were differentially expressed in the Thr-D group relative to Thr-S and Pair-F groups than in the Pair-F group relative to the Thr-S group. KEGG pathway analysis showed that differentially expressed genes were enriched in signal transduction, immune, hormone, lipid, and amino acid metabolism pathways. Our findings indicated that the Thr-D diet increased hepatic triglyceride and fatty acid accumulation via increasing fatty acid and triglyceride synthesis and reducing fatty acid oxidation and triglyceride transport. These findings provide novel insights into our understanding of the molecular mechanisms underlying fat accumulation in the liver caused by dietary threonine deficiency.

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Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.

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Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.

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