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Transcriptome map of the human brain at the single-cell resolution

ABSTRACT: The human brain is about three times larger than the brain of our closest relatives, chimpanzees and bonobos. However, increased size alone fails to explain cognitive abilities unique to humans. Functional changes acquired in the human lineage are likely mediated by divergent gene expression and cell composition in brain regions. Here we generated a map of the human brain transcriptome by assessing the gene expression levels in 33 distinct regions representing all major brain structures from four adult cognitively healthy human individuals, three chimpanzees, three bonobos, and three rhesus macaques. We further conducted single-nuclei RNA-sequencing (SN-seq) experiment in three of the 33 brain regions in four species: two regions showing excess of the human-specific differences, cingulate anterior cortex and cerebellar gray matter, as well as one region showing no such excess, caudate nucleus. We determined cell type specificity of human-specific differences observed in the bulk tissue analysis, and identified species-specific expression differences directly using SN-seq data. This data resource forms a comprehensive baseline for studies of normal and abnormal human brain function and evolution.

ORGANISM(S): Pan troglodytes Pan paniscus Homo sapiens Macaca mulatta

PROVIDER: GSE127774 | GEO | 2020/01/30

REPOSITORIES: GEO

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Transcriptome map of the human brain at the single-cell resolution

Project description:The human brain is about three times larger than the brain of our closest relatives, chimpanzees and bonobos. However, increased size alone fails to explain cognitive abilities unique to humans. Functional changes acquired in the human lineage are likely mediated by divergent gene expression and cell composition in brain regions. Here we generated a map of the human brain transcriptome by assessing the gene expression levels in 33 distinct regions representing all major brain structures from four adult cognitively healthy human individuals, three chimpanzees, three bonobos, and three rhesus macaques. We further conducted single-nuclei RNA-sequencing (SN-seq) experiment in three of the 33 brain regions in four species: two regions showing excess of the human-specific differences, cingulate anterior cortex and cerebellar gray matter, as well as one region showing no such excess, caudate nucleus. We determined cell type specificity of human-specific differences observed in the bulk tissue analysis, and identified species-specific expression differences directly using SN-seq data. This data resource forms a comprehensive baseline for studies of normal and abnormal human brain function and evolution.

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Transcription profiling of human and chimp brain tissues

Project description:We have analyzed gene expression in various brain regions of humans and chimpanzees. Within both human and chimpanzee individuals, the transcriptomes of the cerebral cortex are very similar to each other and differ more between individuals than among regions within an individual. In contrast, the transcriptomes of the cerebral cortex, the caudate nucleus, and the cerebellum differ substantially from each other. Between humans and chimpanzees, 10% of genes differ in their expression in at least one region of the brain. The majority of these expression differences are shared among all brain regions. Whereas genes encoding proteins involved in signal transduction and cell differentiation differ significantly between brain regions within individuals, no such pattern is seen between the species. However, a subset of genes that show expression differences between humans and chimpanzees are distributed nonrandomly across the genome. Furthermore, genes that show an elevated expression level in humans are statistically significantly enriched in regions that are recently duplicated in humans

2010-02-12 | E-AFMX-2 | biostudies-arrayexpress

Evolutionary Significance of DNA Methylation in Human and Chimpanzee Brains

Project description:We compared the genome-wide patterns of DNA methylation in the brains of humans to those of our closest evolutionary relative, chimpanzees, using base-pair resolution whole-genome methylation maps of the prefrontal cortex. Our data reveal that the prefrontal cortex is the most heavily methylated among the human tissues examined so far. Nevertheless, hundreds of genes exhibit dramatically reduced levels of promoter DNA methylation in the human brain relative to the chimpanzee brain. Many of these genes are associated with neurological disorders, psychological disorders, and cancers, and are enriched for functions related to cellular metabolic processes and protein binding. Moreover, the majority of these genes exhibit higher expression in the human brain compared to the chimpanzee brain. Profiling DNA methylation map in prefrontal cortex regions of postmortem brains of three humans and three chimpanzees

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Human-specific features of special gene expression and regulation in eight brain regions

Project description:Despite the substantial efforts made to compile the molecular maps of the human brain, they do not fully inform us of the features unique to humans. Yet, identification of these features might help us to understand both the evolution and nature of the human cognitive traits. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, gibbon and macaques. Integrated analysis of these data revealed existence of 1,851 human-specific transcriptome differences affecting one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than a half of these differences represented elevated expression in human hippocampus, while the rest affected microglial functions in neocortex. Analysis of predicted regulatory interactions driving these differences revealed role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species.

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Evolutionary and ontogenetic changes in RNA editing in human, chimpanzee and macaque brains

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Gene expression in human vs chimpanzees

Project description:Despite the close evolutionary relationship and striking genetic similarity between humans and chimpanzees, there are remarkable differences in anatomy, behavior, and disease susceptibility in the two species. One step towards understanding the biological basis of these phenotypic differences is to characterize quantitative differences in levels of expression of genes in humans and chimpanzees. To contribute to such analysis, we compared gene expression patterns in lymphoblastoid cell lines between nine unrelated humans and ten unrelated chimpanzees by using human cDNA microarrays. Hybridizations to arrays containing 43,233 features produced high quality data for 22,879 cDNA clones, representing 20,266 Unigenes. We observed statistically significant differences in transcript levels for 32% of these genes (P < 0.05, Student t test), with about 200 cDNAs showing differences of more than 2-fold (lower bounds of 95% confidence interval). Among these are genes involved in cell surface glycosylation and responses to toxins and viruses. Examination of functional annotations for the differentially expressed genes revealed lower expression of cell cycle and energy pathways genes, and higher expression of chemokines, 26S proteasome and cell motility genes in chimpanzee samples. These genes and pathways could underlie some of the phenotypic differences between humans and chimpanzees. Keywords: other

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Cell type and species-specific methylation patterns in neuronal and non-neuronal cells of human and chimpanzee cortex

Project description:Using reduced representation bisulfite sequencing (RRBS), we have compared the methylomes of neuronal and non-neuronal cells from three female human and three chimpanzee cortices (Brodmann area 10). Differentially methylated regions (DMRs) with genome-wide significance were enriched in specific chromosomal regions. Intraspecific methylation differences between neuronal and non-neuronal cells were approximately three times more abundant than interspecific methylation differences between human and chimpanzee cell types. The vast majority (>90%) of human intraspecific DMRs (including DMRs with retrotransposons) were hypomethylated in neurons, compared to glia. Intraspecific DMRs were enriched in genes that have been associated with different neuropsychiatric disorders. Interspecific DMRs were enriched in genes showing human-specific brain histone modifications. Methylation differences between human and chimpanzee non-neuronal cells (N=666) were much more frequent than neuronal interspecific DMRs (N=96). More than 95% of interspecific non-neuronal DMRs were hypermethylated in humans.

2018-08-14 | GSE109559 | GEO

Evolutionary and ontogenetic changes in RNA editing in human, chimpanzee and macaque brains

Project description:we used RNA-Seq to quantify the RNA editing level at more than 8,000 previously annotated exonic A-to-I RNA editing sites in two brain regions - prefrontal cortex and cerebellum - of humans, chimpanzees and rhesus macaques. We observed substantial conservation of RNA editing levels between the brain regions, as well as among the three primate species. Evolutionary changes in RNA editing were nonetheless evident among the species. Across lifespan, we observed an increase of the RNA editing level with advanced age in both brain regions of all three primate species. poly(A) enriched RNAs extracted from pooled samples of two brain regions: CBC and PFC of chimpanzee and macaque, fragmented, revers transcribed to double-stranded cDNA using random hexamers. Sequencing libraries were prepared according to the paired-end non-strand-specific sample preparation protocol of Illumina. Each sample was sequenced in a separate lane in the Illumina Genome Analyzer II system, using the 75-bp paired-end sequencing protocol. human data was downloaded from SRA [SRP005169]

2014-01-07 | E-GEOD-45244 | biostudies-arrayexpress

Increased Neanderthal ancestry in genomic regions associated with lipid catabolism in contemporary Europeans

Project description:While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence. 14 human and 6 chimpanzee samples were sequenced.

2014-03-31 | E-GEOD-45263 | biostudies-arrayexpress

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