Post-transcriptional mechanisms distinguish human and chimpanzee forebrain progenitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Pan troglodytes Homo sapiens
PROVIDER: GSE127253 | GEO | 2021/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Post-transcriptional mechanisms distinguish human and chimpanzee forebrain progenitors
| PRJNA524484 | ENA
Project description:Complete genome sequencing has identified millions of DNA changes that differ between humans and chimpanzees. Although a subset of these changes likely underlies important phenotypic differences between humans and chimpanzees, it is currently difficult to distinguish causal from incidental changes and to map specific phenotypes to particular genome locations. To facilitate further genetic study of human-chimpanzee divergence, we have generated human and chimpanzee auto-tetraploids and allo-tetraploids by fusing induced pluripotent stem cells (iPSCs) of each species. The resulting tetraploid iPSCs can be stably maintained and retain the ability to differentiate along ectoderm, mesoderm, and endoderm lineages. RNA sequencing identifies thousands of genes whose expression differs between humans and chimpanzees when assessed in single-species diploid or auto-tetraploid iPSCs. Analysis of gene expression patterns in inter-specific allo-tetraploid iPSCs shows that human-chimpanzee expression differences arise from substantial contributions of both cis-acting changes linked to the genes themselves, and trans-acting changes elsewhere in the genome. To enable further genetic mapping of species differences, we tested chemical treatments for stimulating genome-wide mitotic recombination between human and chimpanzee chromosomes, and CRISPR methods for inducing species-specific changes on particular chromosomes in allo-tetraploid cells. We successfully generated derivative cells with nested deletions or inter-specific recombination on the X chromosome. These studies identify a long distance cis-regulatory domain of the Fragile X-associated gene (FMR1), confirm an important role for the X chromosome in trans-regulation of other expression differences, and illustrate the potential of this system for more detailed mapping of the molecular basis of human and chimpanzee evolution.
2021-11-29 | GSE184768 | GEO
Project description:Human Accelerated Regions (HARs) are highly conserved across species but exhibit a significant excess of human-specific sequence changes, suggesting they may have gained novel functions in human evolution. HARs include gene regulatory elements with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unknown whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. We generated a high-resolution map of chromatin interactions for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs) to comprehensively identify gene targets in both species. HARs and their chimpanzee orthologs targeted a conserved set of 2,963 genes enriched for neurodevelopmental processes including neurogenesis and synaptic transmission. Changes in HAR enhancer activity were correlated with changes in conserved gene target expression. Conserved targets were enriched among genes differentially expressed between human and chimpanzee NSCs or between human and non-human primate developing and adult brain. Species-specific HAR gene targets did not converge on known biological functions and were not significantly enriched among differentially expressed genes, suggesting that most HARs did not alter gene expression via enhancer hijacking. HAR gene targets, including differentially expressed targets, also showed cell type-specific expression patterns in the developing human brain, notably in outer radial glia, which are hypothesized to contribute to human cortical expansion. Our findings support that HARs influenced human brain evolution by altering the expression of a conserved set of gene targets and provide the means to functionally link HARs with novel human brain features.
2024-06-25 | GSE270272 | GEO
Project description:Genome wide DNA methylation profiling of brain and liver from human and chimpanzee. The Illumina HumanMethylation27 DNA Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs for each sample. Samples included liver and NeuN-positive/NeuN-negative/unsorted brain in three individuals from each of two species (human and chimpanzee).
2015-06-19 | GSE38804 | GEO
Project description:mRNA-seq were conducted for iPS cells of human-1 (409-B2/HPS0076), human-2 (Nips-B2/HPS0223), chimpanzee-1 (kiku/0138F-1), and chimpanzee-2 (mari/0274F-2). To compare gene expression levels, the reads were first mapped to the chimpanzee genome (panTro5), and mapped reads were then mapped to the human genome (hg38). Gene expression was anlyzed based on the hg38 annotation.
2022-10-26 | GSE201296 | GEO
Project description:The origin of humans was accompanied by the emergence of new behavioral and cognitive functions, including language and specialized forms of abstract representation. However, the molecular foundations of these human capabilities are poorly understood. Because of the extensive similarity between human and chimpanzee DNA sequences, it has been suggested that many of the key phenotypic differences between species result primarily from alterations in the regulation of genes rather than in their sequences. To characterize gene expression patterns accross the brain and investigate the genetic basis of human specializations in brain organization and cognition, we used microarrays to quantify the transcript levels of thousands of genes in tissue samples from different brain regions of several human and chimpanzee individuals. Our results indicated that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans, and suggests that the human brain is characterized by elevated levels of neuronal activity. Keywords: Species comparative study
2007-04-26 | GSE7540 | GEO
Project description:It has long been hypothesized that changes in gene regulation have played an important role in primate evolution. However, despite the wealth of comparative gene expression data, there are still only few studies that focus on the mechanisms underlying inter-primate differences in gene regulation. In particular, we know relatively little about the degree to which changes in epigenetic profiles might explain differences in gene expression levels between primates. To this end, we studied DNA methylation and gene expression levels in livers, hearts, and kidneys from multiple humans and chimpanzees. Genome wide DNA methylation profiling of heart, kidney, and liver samples from humans and chimpanzees. The Illumina Infinium 27K Human DNA Methylation BeadChip v1.2 was used to compare DNA methylation profiles across approximately 10,575 CpG sites in human and chimpanzee tissue samples. Samples included 6 human livers, 6 human kidneys, 6 human heart, 6 chimpanzee livers, 6 chimpanzee kidneys, and 6 chimpanzee hearts. Two techical replicates of bisulfite converted DNA from each of the 36 samples was hybridized to the Illumina HumanMethylation27 Beadchip. We limited our analysis to the 10,575 probes that were a perfect sequence match to both the human and chimpanzee genomes and which were associated with genes for which we had previously collected expression measurements across the three tissues.
2011-02-25 | E-GEOD-26033 | biostudies-arrayexpress
Project description:Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species. A species experiment design type assays differences between distinct species. Using regression correlation, arrayCGH, acCGH
2006-01-05 | E-GEOD-3980 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of brain and liver from human and chimpanzee. The Illumina HumanMethylation27 DNA Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs for each sample. Samples included liver and NeuN-positive/NeuN-negative/unsorted brain in three individuals from each of two species (human and chimpanzee). Bisulphite converted DNA from the 24 samples were hybridised to the Illumina HumanMethylation27 Beadchip (HumanMethylation27_270596_v.1.2)
2015-06-19 | E-GEOD-38804 | biostudies-arrayexpress
Project description:Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species.
2013-01-30 | E-SMDB-2855 | biostudies-arrayexpress