FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366223546> ?p ?o ?g. }

• W4366223546 abstract "Bipolar disorder (BD) is a chronic mental illness characterized by recurrent episodes of mania and depression and associated with social and cognitive disturbances. Environmental factors, such as maternal smoking and childhood trauma, are believed to modulate risk genotypes and contribute to the pathogenesis of BD, suggesting a key role in epigenetic regulation during neurodevelopment. 5-hydroxymethylcytosine (5hmC) is an epigenetic variant of particular interest, as it is highly expressed in the brain and is implicated in neurodevelopment, and psychiatric and neurological disorders.Induced pluripotent stem cells (iPSCs) were generated from the white blood cells of two adolescent patients with bipolar disorder and their same-sex age-matched unaffected siblings (n = 4). Further, iPSCs were differentiated into neuronal stem cells (NSCs) and characterized for purity using immuno-fluorescence. We used reduced representation hydroxymethylation profiling (RRHP) to perform genome-wide 5hmC profiling of iPSCs and NSCs, to model 5hmC changes during neuronal differentiation and assess their impact on BD risk. Functional annotation and enrichment testing of genes harboring differentiated 5hmC loci were performed with the online tool DAVID.Approximately 2 million sites were mapped and quantified, with the majority (68.8%) located in genic regions, with elevated 5hmC levels per site observed for 3' UTRs, exons, and 2-kb shorelines of CpG islands. Paired t-tests of normalized 5hmC counts between iPSC and NSC cell lines revealed global hypo-hydroxymethylation in NSCs and enrichment of differentially hydroxymethylated sites within genes associated with plasma membrane (FDR = 9.1 × 10-12) and axon guidance (FDR = 2.1 × 10-6), among other neuronal processes. The most significant difference was observed for a transcription factor binding site for the KCNK9 gene (p = 8.8 × 10-6), encoding a potassium channel protein involved in neuronal activity and migration. Protein-protein-interaction (PPI) networking showed significant connectivity (p = 3.2 × 10-10) between proteins encoded by genes harboring highly differentiated 5hmC sites, with genes involved in axon guidance and ion transmembrane transport forming distinct sub-clusters. Comparison of NSCs of BD cases and unaffected siblings revealed additional patterns of differentiation in hydroxymethylation levels, including sites in genes with functions related to synapse formation and regulation, such as CUX2 (p = 2.4 × 10-5) and DOK-7 (p = 3.6 × 10-3), as well as an enrichment of genes involved in the extracellular matrix (FDR = 1.0 × 10-8).Together, these preliminary results lend evidence toward a potential role for 5hmC in both early neuronal differentiation and BD risk, with validation and more comprehensive characterization to be achieved through follow-up study." @default.
• W4366223546 created "2023-04-19" @default.
• W4366223546 creator A5002207849 @default.
• W4366223546 creator A5024967900 @default.
• W4366223546 creator A5032898046 @default.
• W4366223546 creator A5074383128 @default.
• W4366223546 date "2023-04-17" @default.
• W4366223546 modified "2023-10-09" @default.
• W4366223546 title "A pilot investigation of differential hydroxymethylation levels in patient-derived neural stem cells implicates altered cortical development in bipolar disorder" @default.
• W4366223546 cites W1488855101 @default.
• W4366223546 cites W1577094786 @default.
• W4366223546 cites W1836985274 @default.
• W4366223546 cites W1965388596 @default.
• W4366223546 cites W1965710974 @default.
• W4366223546 cites W1976752846 @default.
• W4366223546 cites W1983302342 @default.
• W4366223546 cites W1984190403 @default.
• W4366223546 cites W1984344128 @default.
• W4366223546 cites W1984369088 @default.
• W4366223546 cites W1989457196 @default.
• W4366223546 cites W1990204447 @default.
• W4366223546 cites W1990689143 @default.
• W4366223546 cites W1995885578 @default.
• W4366223546 cites W2011359270 @default.
• W4366223546 cites W2012921410 @default.
• W4366223546 cites W2020016210 @default.
• W4366223546 cites W2021322409 @default.
• W4366223546 cites W2026255880 @default.
• W4366223546 cites W2032475836 @default.
• W4366223546 cites W2037009121 @default.
• W4366223546 cites W2041028481 @default.
• W4366223546 cites W2046812959 @default.
• W4366223546 cites W2047021875 @default.
• W4366223546 cites W2047789918 @default.
• W4366223546 cites W2049006504 @default.
• W4366223546 cites W2051751481 @default.
• W4366223546 cites W2053108849 @default.
• W4366223546 cites W2062655017 @default.
• W4366223546 cites W2067931814 @default.
• W4366223546 cites W2073158583 @default.
• W4366223546 cites W2077867097 @default.
• W4366223546 cites W2079384709 @default.
• W4366223546 cites W2092559397 @default.
• W4366223546 cites W2097342705 @default.
• W4366223546 cites W2107368073 @default.
• W4366223546 cites W2109200753 @default.
• W4366223546 cites W2110319588 @default.
• W4366223546 cites W2114104545 @default.
• W4366223546 cites W2116697224 @default.
• W4366223546 cites W2117495998 @default.
• W4366223546 cites W2122008829 @default.
• W4366223546 cites W2124552698 @default.
• W4366223546 cites W2131467248 @default.
• W4366223546 cites W2133752646 @default.
• W4366223546 cites W2140509910 @default.
• W4366223546 cites W2152451432 @default.
• W4366223546 cites W2152636479 @default.
• W4366223546 cites W2152642144 @default.
• W4366223546 cites W2153836963 @default.
• W4366223546 cites W2159407890 @default.
• W4366223546 cites W2159433569 @default.
• W4366223546 cites W2161210583 @default.
• W4366223546 cites W2173180518 @default.
• W4366223546 cites W2180739129 @default.
• W4366223546 cites W2188035077 @default.
• W4366223546 cites W2210593551 @default.
• W4366223546 cites W2282980633 @default.
• W4366223546 cites W2285074092 @default.
• W4366223546 cites W2287464831 @default.
• W4366223546 cites W2320983896 @default.
• W4366223546 cites W2327618684 @default.
• W4366223546 cites W2332243784 @default.
• W4366223546 cites W2338231408 @default.
• W4366223546 cites W2510734833 @default.
• W4366223546 cites W2517180665 @default.
• W4366223546 cites W2560485956 @default.
• W4366223546 cites W2582611787 @default.
• W4366223546 cites W2603718641 @default.
• W4366223546 cites W2611766868 @default.
• W4366223546 cites W2612011931 @default.
• W4366223546 cites W2734522753 @default.
• W4366223546 cites W2750696266 @default.
• W4366223546 cites W2751884637 @default.
• W4366223546 cites W2787079193 @default.
• W4366223546 cites W2790879726 @default.
• W4366223546 cites W2803933126 @default.
• W4366223546 cites W2910238710 @default.
• W4366223546 cites W2950375827 @default.
• W4366223546 cites W2951005359 @default.
• W4366223546 cites W2952836159 @default.
• W4366223546 cites W2966998620 @default.
• W4366223546 cites W2988821571 @default.
• W4366223546 cites W3012235113 @default.
• W4366223546 cites W3108971791 @default.
• W4366223546 cites W3111867040 @default.
• W4366223546 cites W3134684962 @default.
• W4366223546 cites W3138770880 @default.
• W4366223546 cites W3140009941 @default.
• W4366223546 cites W3155815301 @default.
• W4366223546 cites W3162259891 @default.

• next