A cardinal symptom of Major Depressive Disorder (MDD) is the disruption of circadian patterns. Yet, to date, there is no direct evidence of circadian clock dysregulation in the brains of MDD patients. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain was difficult to characterize. Here we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-hour cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses ('Controls') and 34 MDD patients. Our dataset covered ~12,000 transcripts in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (AnCg), hippocampus (HC), amygdala (AMY), nucleus accumbens (NAcc) and cerebellum (CB). Several hundred transcripts in each region showed 24-hour cyclic patterns in Controls, and >100 transcripts exhibited consistent rhythmicity and phase-synchrony across regions. Among the top ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERB), DBP, BHLHE40(DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in MDD brains, due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This is the first transcriptome-wide analysis of cyclic patterns in the human brain and demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggest novel molecular targets for treatment of mood disorders.
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.
Sex, Specimen part, Treatment
View SamplesThe strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Illumina (RatRef-12v1 Beadchip) microarray study examined gene expression in the hippocampus in generation F15 male bHR rats and bLR rats at age postnatal day 14 (P14, n=6 per group).
Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.
Sex, Specimen part
View SamplesRNA-seq profiling was conducted on clinically-annotated human post-mortem brain tissues Overall design: We measured the transcriptome in 281 clinically-annotated human post-mortem brain tissues
Post-mortem molecular profiling of three psychiatric disorders.
Sex, Specimen part, Race, Subject
View SamplesWe used microarrays to globally profile the gene expression changes observed after 24h when transfecting antisense oligonucleotides in HuH77 cells
Managing the sequence-specificity of antisense oligonucleotides in drug discovery.
Treatment
View SamplesRNA sequencing analysis of gene expression in serrated colon polyps, uninvolved colon and control colon Overall design: 86 colon RNA sequencing datasets (21 sessile serrated adenomas/polyps, 10 hyperplastic polyps, 10 adenomatous polyps, 21 uninvolved colon, 20 control colon and 4 colon cancer)
Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype.
No sample metadata fields
View SamplesThe recently released Affymetrix Human Gene 1.0 ST array has two major differences compared with standard 3' based arrays: (1) it interrogates the entire mRNA transcript, and (2) it uses cDNA targets. To assess the impact of these differences on array performance, we performed series of comparative hybridizations between the Human Gene 1.0 ST and the Affymetrix HG-U133 Plus 2.0 and the Illumina HumanRef-8 BeadChip arrays. Additionally, both cRNA and cDNA targets were probed on the HG-U133 Plus 2.0 array. The results show that the overall reproducibility is best using the Gene 1.0 ST array. When looking only at the high intensity probes, the reproducibility of the Gene 1.0 ST array and the Illumina BeadChip array is equally good. Concordance of array results was assessed using different inter-platform mappings. The Gene 1.0 ST is most concordant with the HG-U133 array hybridized with cDNA targets, thus showing the impact of the target type. Agreements are better between platforms with designs which choose probes from the 3' end of the gene. Overall, the high degree of correspondence provides strong evidence for the reliability of the Gene 1.0 ST array.
Affymetrix Whole-Transcript Human Gene 1.0 ST array is highly concordant with standard 3' expression arrays.
No sample metadata fields
View SamplesArabidopsis is a non-host to the biotrophic fungus Blumeria graminis f.sp. hordei (Bgh), effectively hindering Bgh ingress to the epidermal cells by deposition of callosic papillae formations, i.e. penetration resistance. To better understand the transcriptional changes in Arabidopsis towards Bgh, we compared un-inoculated and inoculated wild-type Arabidopsis samples, with those an ATAF1 mutant allele, compromised in penetration resistance. The experiment included sampling of 8 rosettes for each replicate sample from 6-weeks old plants, 12 hrs after inoculation. A total of 12 biolocigal replicates were sampled with three replicates from each of the four blocks (Wild-type, ataf1-1, Bgh, control). ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Michael Krogh Jensen. The equivalent experiment is AT31 at PLEXdb.]
Transcriptional regulation by an NAC (NAM-ATAF1,2-CUC2) transcription factor attenuates ABA signalling for efficient basal defence towards Blumeria graminis f. sp. hordei in Arabidopsis.
No sample metadata fields
View SamplesThe zebrafish is a powerful model for the study of hematopoietic stem and progenitor cells (HSPC). We have developed a novel HSPC-specific transgenic line (Runx1+23:GFP). We have used this line in time-lapse live imaging studies to track the migration of HSPC during development. We have also performed a chemical genetic screen to find small molecules that modulate HSPC numbers during development. Treating embryos from 2-3 days post fertilization (2-3 dpf) then fixing for in situ staining with HSPC probes cmyb and runx1, we found the compound lycorine increased HSPC numbers. Applying this compound during time-lapse live imaging showed increased accumulation of Runx+ HSPC in the caudal hematopoietic tissue (CHT). Treatment from 2-3 dpf, then washing off the compound, had a sustained effect on the size of the HSPC with Runx+ numbers higher at 5 and 7 dpf.
Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche.
Specimen part, Treatment
View SamplesRNA-sequencing of SSP RNA from patients with serrated polyposis syndrome identifies VSIG1 and MUC17 as potential diagnostic markers for SSPs Overall design: 5'' capped RNA from seven ascending SSPs, six patient matched uninvolved right colon and two normal right colon samples was used for RNA sequencing (15 samples total)
RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers.
Sex, Disease, Subject
View Samples