Project description:Post mortem human brain tissue comparison between HD patients and controls from 3 brain regions - cerebellum, frontal cortex [BA4, BA9] and caudate nucleus. Gene expression analysed using linear models from LIMMA package in Bioconductor suite. Keywords: disease state analysis
Project description:Post mortem human brain tissue comparison between HD patients and controls from 3 brain regions - cerebellum, frontal cortex [BA4, BA9] and caudate nucleus. Gene expression analysed using linear models from LIMMA package in Bioconductor suite. Experiment Overall Design: Large sample sizes were used to examine brain tissue gene expression at various stages of HD pathology. Three brain regions were profiled, compared and analysed for differential gene expression. The broad aim was to capture early stage gene expression changes in HD brains.
Project description:4 samples from 9 brain regions Brain tissue from the New South Wales Tissue Resource Centre, 9 brain regions, 4 samples each: 1 male alcoholic, 1 female alcoholic, 1 male control, 1 female control. Brain regions: pre-frontal cortex, cerebral cortex, visual cortex, thalamus, hippocampus, amygdala, caudate nucleus, putamen, cerebellum
Project description:The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of human tissues and to relate it to chronological age. Toward this end, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928 Human DNA methylation Beadchip v1.2 was used to obtain n=260 Illumina DNA methylation array from the following human Brain regions: caudate nucleus (n=n=12), cingulate gyrus (n=n12), cerebellum (n=32), frontal cortex (n=41), hippocampus (n=25), midBrain (n=18), motor cortex (n=33), occipital cortex (n=33), parietal lobe (n=23), sensory cortex (n=12), temporal cortex (n=29), visual cortex (n=11).
Project description:Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease with a fatal outcome. There is accumulating evidence of a prominent role of glia in the pathology of HD, and we investigated this by conducting single nuclear RNA sequencing (snRNAseq) of human post mortem brain in four differentially affected regions; caudate nucleus, frontal cortex, hippocampus and cerebellum. Across 127,205 nuclei from donors with HD and age/sex matched controls, wefound heterogeneity of glia which is altered in HD. We describe prominent changes in the abundance of certain subtypes of astrocytes, microglia, oligodendrocyte precursor cells and oligodendrocytes between HD and control samples, and these differences are widespread across brain regions. Furthermore, we highlight possible mechanisms that characterise the glial contribution to HD pathology including depletion of myelinating oligodendrocytes, an oligodendrocyte-specific upregulation of the calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1A (PDE1A) and an upregulation of molecular chaperones as a cross-glial signature and a potential adaptive response to the accumulation of mutant huntingtin (mHTT). Our results support the hypothesis that glia have an important role in the pathology of HD, and show that all types of glia are affected in the disease.
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:Oxford Nanopore direct RNA sequencing (DRS) can quantify isoform expression, modifications and polyA tail lengths, enabling simultaneous investigation of the transcriptome and epitranscriptome. We applied DRS to three post-mortem human brain regions: prefrontal cortex, caudate nucleus and cerebellum.
Project description:m6A-seq was performed on 4 brain regions (cortex, cerebellum, hypothalmus and hippocampus) of 2 week, 4 week, 6 week, 26 week and 52 week old BL6 mice. m6A profiling was also performed on human adolescent and old brain tissue (region BA9). m6A-seq was also performed on WT and 5xFAD mice (Alzheimer).
Project description:We sought to define and compare the diversity of cells across many brain areas, including various white matter (WM) regions, the volume and complexity of which is limited in mouse brain. We employed magnetic resonance (MR) image-guided sampling and snRNA-seq to survey the transcriptome at cellular resolution. Tissue types included WM (frontal, parietal, temporal), corpus callosum (anterior, posterior), optic tract, cerebral cortex (frontal, parietal, temporal, occipital, cingulate), caudate, hippocampus, lateral geniculate nucleus, cerebellum, thalamus, midbrain, pons, and cervical spinal cord. We profiled nuclei from confined regions (cylinders of tissue 2 mm in diameter and 3 mm in height, ~10 μL), which can be consistently located and repeated based on MR images from animal to animal. We analyze and discuss the global landscape of neural cell types across brain regions, comparing compositional differences of subpopulations of glia in GM and WM, modeling intercellular communication in each milieu, and cataloging their contributions to neurological disorders.