Project description:Gene expression profile at single cell level of striatal cells from the caudate nucleus and putamen in postmortem human brains of unaffected individuals or those with opioid use disorder.
Project description:Background: Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals suffering with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances to sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis. Methods: Here, we perform RNA-sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (NAc, caudate, and putamen) in subjects with psychosis relative to unaffected comparison subjects. Results: Across regions, we find differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens (NAc), mitochondrial-related transcripts have decreased expression in psychosis subjects, but only in those who died at night. Additionally, we find a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the NAc of psychosis subjects. Between region comparisons indicate that rhythmicity in the caudate and putamen is far more similar in subjects with psychosis than in matched comparison subjects. Conclusions: Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.
Project description:Cap analysis of gene expression (CAGE) and massive parallel sequencing were used to profile the promoterome of aged human brains from five regions, namely: caudate, frontal cortex, hippocampus, putamen and temporal cortex. 25 RNA libraries from post-mortem brain tissue (five caudate, five frontal, 5 hippocampus, 5 putamen, five temporal RNA libraries from seven individuals) were processed using CAGE protocol and CAGE tags derived from the 25 libraries were sequenced with Illumina.
Project description:We analyzed transcriptome differences in postmortem caudate and putamen from controls (n=40) and PD (n=35) as confirmed by autopsy. Further, we analyzed region specific differences in caudate and putamen associated with clinical variables.
Project description:The ability to use blood to predict the outcomes of Parkinson’s disease (PD), including disease progression and development of cognitive and motor complications, would be of enormous clinical value. We undertook deep RNA sequencing from the caudate and putamen of postmortem PD (n=35) and control (n=40) striatum, and compared molecular profiles with clinical features, and samples obtained from antemortem peripheral blood from an independent cohort. Cognitive and motor complications of PD were associated with molecular changes in the caudate (e.g., stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset PD were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence) respectively. Molecular signatures in the postmortem PD brain were also evident in antemortem peripheral blood, and correlated with clinical disease features. Together, these findings identify molecular signatures in PD patients' brain and blood of potential pathophysiologic and prognostic importance
Project description:Analysis of gene-expression changes in depressed subjects with bipolar disorder compared to healthy controls. Results provide information on pathways that may be involved in the pathogenesis of bipolar depression. Total RNA isolated from PAXgene blood RNA tubes from 20 depressed subjects with bipolar disorder and 15 healthy controls.
Project description:Comparison of single cell RNAseq and single nucleus RNAseq on four healthy human liver caudate lobes, with cell-types validated using one slice of a fifth healthy human for VISIUM Spatial Transcriptomics. Raw UMI count tables can be found here: https://figshare.com/projects/Human_Liver_SC_vs_SN_paper/98981 Processed Seurat Objects can be found here: https://www.dropbox.com/sh/sso15ehqmrrh6mk/AACKHOsSlZW0_Zy9cbCkOmMfa?dl=0
Project description:RNAseq was performed on caudate, putamen, and substantia nigra samples from animals treated with MPTP to induce a Parkinson's-like condition, and then transplanted with hpNSCs or control buffer. The goal of the study was to determine if there were any difference in gene expression caused by the transplanted cells.
