Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [RNA-Seq]

ABSTRACT: The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type–specific regulatory landscapes in the cortex re- main largely unexplored. Here we report epigenomic and tran- scriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome- wide profiling of the H3K27ac histone modification, we identify neuron-subtype–specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regula- tory changes are uncovered in multiple genes, including those as- sociated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a sub- stantial fraction of pan-neuronal regulatory elements undergos subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell- type–dependent gene-expression programs, and provides a re- source for further exploration of human brain evolution and function.

ORGANISM(S): Pan troglodytes Macaca mulatta

PROVIDER: GSE158932 | GEO | 2020/10/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [ChIP-Seq]

Project description:The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type–specific regulatory landscapes in the cortex re- main largely unexplored. Here we report epigenomic and tran- scriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome- wide profiling of the H3K27ac histone modification, we identify neuron-subtype–specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regula- tory changes are uncovered in multiple genes, including those as- sociated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a sub- stantial fraction of pan-neuronal regulatory elements undergos subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell- type–dependent gene-expression programs, and provides a re- source for further exploration of human brain evolution and function.

2020-10-03 | GSE158931 | GEO

Single Cell Methylome Signatures Reveal Distinct Neuronal Populations and Regulatory Elements in the Mammalian Cortex

Project description:The mammalian brain contains diverse neuron cell types with distinct physiological, morphological and molecular characteristics. However, a comprehensive assessment of the epigenetically distinct neuronal classes is currently missing. Cytosine DNA methylation is a stable epigenetic mark that distinguishes neuron types and marks gene regulatory elements. We developed an efficient single-nucleus methylome sequencing approach that allows robust high-throughput neuron-type classification. We generated >6,000 single-nucleus methylomes and identified 16 mouse and 21 human neuronal subpopulations in the frontal cortex. Both CG and non-CG methylation exhibited cell type-specific distributions that recapitulate and extend findings from single neuron transcriptome profiling. Moreover, we found approximately 500,000 neuron-type-specific regulatory elements showing strong differential methylation in mouse and human cortex. Distinct methylation signatures identified an unique human Parvalbumin-expressing inhibitory sub-type and a layer 6 specific excitatory sub-type in mouse. Comparative epigenomic analysis showed stronger conservation of gene regulatory elements in inhibitory compared with excitatory neurons. These findings demonstrate the utility of single nucleus methylome profiling for both expanding the atlas of brain cell types and identifying regulatory elements that potentially drive these differences.

2017-08-10 | GSE97179 | GEO

Accelerated evolution of oligodendrocytes in human brain

Project description:Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in oligodendrocytes and show that oligodendrocytes have undergone accelerated gene expression evolution in the human lineage. The signature of acceleration is enriched for cell type-specific expression alterations in schizophrenia. These results underscore the importance of oligodendrocytes in human brain evolution.

2019-12-31 | GSE123936 | GEO

Cell type-specific transcriptional programs in mouse prefrontal cortex during adolescence and addiction

Project description:Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Yet, the specific transcriptional programs in each neuron subtype remain unknown. Using single-cell RNA sequencing (scRNA-seq), here we comprehensively classified all unique cell subtypes in the PFC. We analyzed transcriptional dynamics of each cell subtype under a naturally adaptive and an induced condition. Adaptive changes during adolescence (between P21 and P60), a highly dynamic phase of postnatal neuroplasticity, profoundly impacted transcription in each neuron subtype, including cell type-specific regulation of genes implicated in major neuropsychiatric disorders. On the other hand, an induced plasticity evoked by chronic cocaine addiction resulted in progressive transcriptional changes in multiple neuron subtypes and became most pronounced upon prolonged drug withdrawal. Our findings lay a foundation for understanding cell type-specific postnatal transcriptional dynamics under normal PFC function and in neuropsychiatric disease states.

2019-08-29 | GSE124952 | GEO

Sequential regulation of glutamatergic and subtype-specific projection neuron identities in the developing cerebral cortex

Project description:Sequential regulation of glutamatergic and subtype-specific projection neuron identities in the developing cerebral cortex

| PRJNA596452 | ENA

Repurposing of promoters and enhancers during mammalian evolution

Project description:The spatiotemporal control of gene expression exerted by promoters and enhancers is central for organismal development, physiology and behaviour. These two types of regulatory elements have long been distinguished from each other based on their function, but recent work highlighted common architectural and functional features. It also suggested that inheritable alterations in the epigenetic and sequence context of regulatory elements might underlie evolutionary changes of their principal activity, which could result in changes in the transcriptional profile of genes under their control or even facilitate the birth of new genes. Here, based on integrated cross-mammalian analyses of DNase hypersensitivity, chromatin modification and transcriptional data, we provide support for this hypothesis by detecting 445 regulatory elements with signatures of activity turnover in sister species from the primate and rodent lineages (termed "P/E" elements). Through the comparison with outgroup species, we defined the directionality of turnover events, which revealed that most instances represent transformations of putative ancestral enhancers into promoters, leading to the emergence of species-specific transcribed loci or 5' exons. Notably, P/E elements have distinct GC sequence compositions and stabilizing 5' splicing (U1) regulatory motif patterns, which may predispose them to functional repurposing during evolution. Moreover, we trace changes in the U1 and polyadenylation signal densities and distributions that accompanied and likely drove the evolutionary activity switches. Overall, our work highlights functional repurposing as a notable mechanism that likely facilitated regulatory innovation and the origination of new genes and exons during mammalian evolution.

2018-10-01 | GSE114191 | GEO

Mapping active promoters by ChIP-seq profiling of H3K4me3 in cichlid fish - a first step to uncover cis-regulatory elements in ecological model teleosts

Project description:Evolutionary alterations to cis-regulatory sequences are likely to cause adaptive phenotypic complexity, through orchestrating changes in cellular proliferation, identity and communication. For non-model organisms with adaptive key-innovations, patterns of regulatory evolution have been predominantly limited to targeted sequence-based analyses. Chromatin-immunoprecipitation with high-throughput sequencing (ChIP-seq) is a technology that has only been used in genetic model systems and is a powerful experimental tool to screen for active cis-regulatory elements. Here, we show that it can also be used in ecological model systems and permits genome-wide functional exploration of cis-regulatory elements. As a proof of concept, we use ChIP-seq technology in adult fin tissue of the cichlid fish Oreochromis niloticus to map active promoter elements, as indicated by occupancy of trimethylated Histone H3 Lysine 4 (H3K4me3). The fact that cichlids are one of the most phenotypically diverse and species-rich families of vertebrates could make them a perfect model system for the further in-depth analysis of the evolution of transcriptional regulation. examination of H3K4me3 in adult fin tissue of the Nile tilapia (Oreochromis niloticus)

2015-07-07 | E-GEOD-62791 | biostudies-arrayexpress

Accelerated functional evolution of regulatory lncRNAs in the human lineage

Project description:Long noncoding RNA sequences evolve relatively rapidly, but it is unclear whether this is due to relaxed constraint or accelerated evolution. Here, we trace the recent evolutionary history of human lncRNAs, using genomes of multiple individuals from all great ape species to map fixed lineage-specific nucleotide variants. We find that the lower conservation of lncRNAs compared to protein coding genes partially arises from lncRNA’s more recent evolutionary origin. We identify more than one hundred lncRNAs that show some evidence of accelerated evolution in at least one primate species, including 17 in human. Several of these display transcriptional regulatory activity in an RNA-specific reporter assay. By experimentally reconstructing the ancestral lncRNA sequence, we find that this activity has been altered by human-specific nucleotide substitutions. Functional analysis of accelerated lncRNAs with specific expression in blood suggests lncRNAs have participated in adaptive regulatory changes in the immune system during recent human evolution. Together our results provide evidence that accelerated evolution of lncRNAs may have contributed, through regulatory changes, to human-specific phenotypes.

2018-11-30 | GSE80554 | GEO

MicroRNA expression in primate postnatal brain through lifespan

Project description:While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such change remain poorly understood. Here we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpanzees and humans throughout their lifespan. We find that developmental profiles of trans-regulators, such as miRNA, as well as their target genes, show the fastest rates of human-specific evolutionary change. Changes in expression of a few key regulators may be a major driving force behind human brain evolution. Human, chimpanzee and rhesus macaque post-mortem brain samples from the prefrontal cortex and cerebellar cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to B72.

2011-12-09 | E-GEOD-29356 | biostudies-arrayexpress

Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate motor cortex

Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes, and that epigenetic status at distal candidate cis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species, and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity help uncover functional cis-regulatory elements and enhance our ability to interpret genetic variants contributing to neurological disease and traits.

2023-10-31 | GSE229169 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data