title: Transcriptome profiling of human hippocampus dentate gyrus granule cells in mental illness.
abstract: This study is, to the best of our knowledge, the first application of whole transcriptome sequencing (RNA-seq) to cells isolated from postmortem human brain by laser capture microdissection. We investigated the transcriptome of dentate gyrus (DG) granule cells in postmortem human hippocampus in 79 subjects with mental illness (schizophrenia, bipolar disorder, major depression) and nonpsychiatric controls. We show that the choice of normalization approach for analysis of RNA-seq data had a strong effect on results; under our experimental conditions a nonstandard normalization method gave superior results. We found evidence of disrupted signaling by miR-182 in mental illness. This was confirmed using a novel method of leveraging microRNA genetic variant information to indicate active targeting. In healthy subjects and those with bipolar disorder, carriers of a high- vs those with a low-expressing genotype of miR-182 had different levels of miR-182 target gene expression, indicating an active role of miR-182 in shaping the DG transcriptome for those subject groups. By contrast, comparing the transcriptome between carriers of different genotypes among subjects with major depression and schizophrenia suggested a loss of DG miR-182 signaling in these conditions.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kohen
authors.affiliation: 1] Department of Statistics, University of Washington, Seattle, WA, USA [2] Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA, USA [3] Center for Statistics and The Social Sciences, University of Washington, Seattle, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dobra
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Tracy
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Haugen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000592:standards; D005838:Genotype; D006801:Humans; D061346:Laser Capture Microdissection / Q000379:methods; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D014015:Tissue Banks; D059467:Transcriptome / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C538984:Mirn182 microRNA, human