Cell type and species-specific methylation patterns in neuronal and non-neuronal cells of human and chimpanzee cortex
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens Pan troglodytes
PROVIDER: GSE109559 | GEO | 2018/08/14
REPOSITORIES: GEO
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Project description:Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. Here, we use induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration and early development of cortical pyramidal neurons in humans and chimpanzees. In addition, we provide morphological characterization of the early stages of neuronal development in human and chimpanzee transplanted cells, and examine the role of developmental mechanisms previously proposed for the evolutionary expansions of the human brain on the early development of pyramidal neurons in the two species. The strategy proposed here lay down the basis for further comparative analysis between human and non-human primates and opens new avenues for understanding cognitive capability and neurological disease susceptibility differences between species. PolyA RNA-Seq profiling of neural progenitor cells (NPCs) and neurons differentiated from human and chimpanzee iPSCs.
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Project description:We search for developmental changes specific to humans by examining gene expression profiles in the human, chimpanzee and rhesus macaque prefrontal and cerebellar cortex. In both brain regions, developmental patterns were more evolved in humans than in chimpanzees. The major human specific genes in prefrontal cortex was enriched in neuronal functions and regulated by several transcription factors, which were previously implicated in regulation of neuronal functions. To confirm neuronal function of the human prefrontal cortex specific genes, we identifed response genes upon neuronal activation in mouse cortical neurons. Our results show that human specific genes are enriched in the response genes upon neuronal activation, implying the function of human prefrontal cortex specific genes in synaptic development. The cortical neurons from E15 mouse were isolated and cultured. We then exposed neurons to bicuculline (Bic), or potassium chloride (KCl), or without treatment. The cultured neurons under each group were hybridized to Agilent whole mouse genome oligo microarray (4x44k).
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Project description:Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. Here, we use induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration and early development of cortical pyramidal neurons in humans and chimpanzees. In addition, we provide morphological characterization of the early stages of neuronal development in human and chimpanzee transplanted cells, and examine the role of developmental mechanisms previously proposed for the evolutionary expansions of the human brain on the early development of pyramidal neurons in the two species. The strategy proposed here lay down the basis for further comparative analysis between human and non-human primates and opens new avenues for understanding cognitive capability and neurological disease susceptibility differences between species.
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Project description:Cell type and species-specific methylation patterns in neuronal and non-neuronal cells of human and chimpanzee cortex
| PRJNA431394 | ENA
Project description:In this work, we evaluated the genetic stabilization process, of the intra- (Saccharomyces cerevisiae) and interspecific (S. cerevisiae x Saccharomyces kudriavzevii) hybrids obtained by different non-GMO techniques, under fermentative conditions. Large-scale transitions in genome size, detected by measuring total DNA content, and genome reorganizations in both nuclear and mitochondrial DNA, evidenced by changes in molecular markers, were observed during the experiments. Interspecific hybrids seem to need fewer generations to reach genetic stability than intraspecific hybrids. The largest number of molecular patterns among the derived stable colonies was observed for intraspecific hybrids, particularly for those obtained by rare-mating in which the total amount of initial DNA was larger. Finally, a representative intraspecific stable hybrid underwent a normal industrial process to obtain active dry yeast production as an important point at which inducing changes in genome composition was possible. No changes in hybrid genetic composition after this procedure were confirmed by comparative genome hybridization. According to our results, fermentation steps 2 and 5 –comprising between 30 and 50 generations- suffice to obtain genetically stable interspecific and intraspecific hybrids, respectively. This work aimed to develop and validate a fast genetic stabilization method for newly generated Saccharomyces hybrids under selective enological conditions. A comparison of the whole stabilization process in intra- and interspecific hybrids showing different ploidy levels, as a result of using different hybridization methodologies, was also made. A stable hybrid strain was compared with itself before and after ADY (active dry yeast) production in order to evaluate the genetic stability of this strain.
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Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness.
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