Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1060740 | ENA |
REPOSITORIES: ENA
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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
Project description:Dissecting the Individual and Collective Regenerative Behavior of Muscle Stem Cells During Aging
| PRJNA497842 | ENA
Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of the 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 helps uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.
2023-11-15 | GSE241339 | GEO
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.
2023-11-28 | GSE246760 | GEO
Project description:Sequence divergence of cis-regulatory elements drives species-specific traits, but how this manifests in the evolution of the 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 helps uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.
2023-10-31 | GSE240297 | GEO
Project description:Genes not only control traits of their carrier organism (known as Direct Genetic Effects or DGEs) but also shape their carrier's physical environment and the phenotypes of their carrier's social partners (known as Indirect Genetic Effects or IGEs). Theoretical research has shown that the effects that genes exert on social partners can have profound consequences, potentially altering heritability and the direction of trait evolution. Complementary empirical research has shown that in various contexts (particularly in animal agriculture) IGEs can explain a large proportion of variation in specific traits. However, little is known about the general prevalence of IGEs. We conducted a reciprocal cross-fostering experiment with two genetic lineages of the clonal raider ant Ooceraea biroi to quantify the relative contribution of DGEs and IGEs to variation in brain gene expression (which underlies behavioral variation). We find that thousands of genes are differentially expressed by DGEs but not a single gene is differentially expressed by IGEs. This is surprising given the highly social context of ant colonies and given that individual behavior varies according to the genotypic composition of the social environment in O. biroi. Overall, these findings indicate that we have a lot to learn about how the magnitude of IGEs varies across species and contexts.
2022-08-29 | GSE210246 | GEO
Project description:Inter-patient and intra-tumoral heterogeneity complicate the identification of predictive biomarkers and effective treatments for basal triple negative breast cancer (b-TNBC). Invasion is the initiating event in metastasis and can occur by both collective and single-cell mechanisms. We cultured primary organoids from a b-TNBC genetically engineered mouse model in 3D collagen gels to characterize their invasive behavior. We observed that organoids from the same tumor presented different phenotypes that we classified as non-invasive, collective and disseminative. To identify molecular regulators driving these invasive phenotypes, we developed a workflow to isolate individual organoids from the collagen gels based on invasive morphology and perform RNA sequencing. We next tested the requirement of differentially regulated genes for invasion using shRNA knock-down. Strikingly, KRAS was required for both collective and disseminative phenotypes. We then performed a drug screen targeting signaling nodes upstream and downstream of KRAS. We found that inhibition of EGFR, MAPK/ERK, or PI3K/AKT signaling reduced invasion. Of these, ERK inhibition was striking for its ability to potently inhibit collective invasion and dissemination. We conclude that different cancer cells in the same b-TNBC tumor can express different metastatic molecular programs and identified KRAS and ERK as essential regulators of collective and single cell dissemination.
2023-01-03 | GSE215069 | GEO
Project description:Collective behavior and virulence arsenal of Piscirickettsia salmonis biofilms
| PRJEB53864 | ENA
Project description:The transition to parasitism is a drastic shift in lifestyle, involving rapid changes in gene structure, function, and expression. Evolutionarily 'young' parasites are ideal models for the elucidation of the early steps of this transition. After the establishment of an antagonistic relationship, parasite and host co-evolve through reciprocal adaptations resulting in an evolutionary arms-race. Repeated evolution of social parasitism and slavery among Temnothorax ants allows us to examine gene expression patterns characterizing slavemaker raiding and reciprocal host defensive behavior. Previous studies of Temnothorax provide evidence for co-evolving adaptations between parasites and hosts, as well as diverging raiding strategies between slavemakers. However, under parasite pressure, host defense portfolios shift similarly, suggesting diverging evolution of defensive traits. Through comparative gene expression analyses, we find that slavemaker raiding behavior is characterized by a down-regulation of numerous genes relative to their non-raiding state. Moreover, only a small number of genes shared expression between slavemaking species. In contrast, hosts possess a higher ratio of commonly-to-privately over-expressed genes and metabolic pathways during raids, suggesting that genes of similar function control defensive behavior. Additionally, a number of candidate genes were identified, each potentially playing a major role in shaping slavemaker- and host-specific behaviors. Finally, in two slavemaking species, functional enrichment analyses indicate that genes over-expressed during raiding behavior are associated with ribosomal structure, oxidation-reduction, and metabolic processes. Overall, our analysis revealed evidence for divergent evolution among closely-related ant species, where species-specific gene expression characterize raiding and defensive behavior.
2017-07-01 | GSE95604 | GEO
Project description:In a rapidly warming world, exposure to high temperatures may impact fitness, but the gene regulatory mechanisms that link sublethal heat to sexually selected traits are not well understood, particularly in endothermic animals. Our experiment used zebra finches (Taeniopygia guttata), songbirds that experience extreme temperature fluctuations in their native Australia. We exposed captive males to an acute thermal challenge (43°C) compared with thermoneutral (35°C) and lower (27°C) temperatures. We found significantly more heat dissipation behaviors at 43°C and heat retention behaviors at 27°C, temperatures previously shown to reduce song production and fertility. Next, we characterized gene expression in tissues important for mating effort – the posterior telencephalon, for its role in song production, and the testis, for its role in fertility and hormone production. Differential expression of hundreds of genes in the testes, but few in the brain, suggest the brain is more buffered from extreme temperatures. Nevertheless, dopaminergic signaling in the brain co-varied with heat dissipation behaviors, providing a mechanism by which temporary thermal challenges may alter motivational circuits for song production. In both brain and testis, we also observed quantitative continuous variation between thermally sensitive gene networks and individual differences in thermoregulatory behavior, indicating that mechanisms of thermal-behavioral tolerance have microevolutionary potential. Taken together, these results suggest that selection for thermal tolerance could impact performance of sexually selected traits, and in turn, sexual selection in a warming world could influence how thermal tolerance evolves.
2022-10-01 | GSE185196 | GEO