Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1081293 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28116071_1.fastq.gz | Fastqsanger.gz | |||
| SRR28116071_2.fastq.gz | Fastqsanger.gz | |||
| SRR28116072_1.fastq.gz | Fastqsanger.gz | |||
| SRR28116072_2.fastq.gz | Fastqsanger.gz | |||
| SRR28116073_1.fastq.gz | Fastqsanger.gz |
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Project description:Human brain development starts during embryogenesis and extends postnatally to adulthood. During this time, the cellular complexity of the brain is established via dynamic changes in gene expression, mediated, in part, by the spatiotemporal activity of cis-regulatory elements. To better understand these processes, we performed simultaneous profiling of gene expression and chromatin accessibility in 45,549 individual nuclei, isolated from the human cortex across 6 broad developmental time-points from fetus to adult. We identified cell-type specific domains in which chromatin accessibility is highly correlated with gene expression. Differentiation pseudotime trajectories of gene expression in neuronal subpopulations indicate that chromatin accessibility at cis-regulatory elements precedes transcription and that dynamic changes in chromatin structure play a critical role in neuronal lineage commitment. In addition, using lineage-specific genes and peaks, we mapped cell-type specific genetic loci implicated in neuropsychiatric traits, including schizophrenia, major depressive disorder and bipolar disorder. Together, our results describe the complex regulation of cell composition at critical stages in lineage determination, serve as a developmental blueprint of the human brain and shed light on the impact of spatiotemporal alterations in gene expression on neuropsychiatric disease.
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Project description:Suspended animation (e.g. hibernation, diapause) allows organisms to survive extreme environments. But the mechanisms underlying the evolution of suspended animation states are unknown. The African turquoise killifish has evolved diapause as a form of suspended development to survive the complete drought that occurs every summer. Here, we show that gene duplicates – paralogs – exhibit specialized expression in diapause compared to normal development in the African turquoise killifish. Surprisingly, paralogs with specialized expression in diapause are evolutionarily very ancient and are present even in vertebrates that do not exhibit diapause. To determine if evolution of diapause is due to the regulatory landscape rewiring at ancient paralogs, we assessed chromatin accessibility genome-wide in fish species with or without diapause. This analysis revealed an evolutionary recent increase in chromatin accessibility at very ancient paralogs in African turquoise killifish. The increase in chromatin accessibility is linked to the presence of new binding sites for transcription factors, likely due to de novo mutations and transposable element (TE) insertion. Interestingly, accessible chromatin regions in diapause are enriched for lipid metabolism genes, and our lipidomics studies uncover a striking difference in lipid species in African turquoise killifish diapause, which could be critical for long-term survival. Together, our results show that diapause likely originated by repurposing pre-existing gene programs via recent changes in the regulatory landscape. This work raises the possibility that suspended animation programs could be reactivated in other species for long-term preservation via transcription factor remodeling and suggests a mechanism for how complex adaptations evolve in nature.
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Project description:Human brain development starts during embryogenesis and extends postnatally to adulthood. During this time, the cellular complexity of the brain is established via dynamic changes in gene expression, mediated, in part, by the spatiotemporal activity of cis-regulatory elements. To better understand these processes, we performed simultaneous profiling of gene expression and chromatin accessibility in 45,549 individual nuclei, isolated from the human cortex across 6 broad developmental time-points from fetus to adult. We identified cell-type specific domains in which chromatin accessibility is highly correlated with gene expression. Differentiation pseudotime trajectories of gene expression in neuronal subpopulations indicate that chromatin accessibility at cis-regulatory elements precedes transcription and that dynamic changes in chromatin structure play a critical role in neuronal lineage commitment. In addition, using lineage-specific genes and peaks, we mapped cell-type specific genetic loci implicated in neuropsychiatric traits, including schizophrenia, major depressive disorder and bipolar disorder. Together, our results describe the complex regulation of cell composition at critical stages in lineage determination, serve as a developmental blueprint of the human brain and shed light on the impact of spatiotemporal alterations in gene expression on neuropsychiatric disease.
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Project description:Understanding the origin of morphological diversity across vertebrates is central to evolutionary developmental biology. cis-regulatory elements (CRE) such as enhancers and promoters interpret precise spatiotemporal cues to control and coordinate gene expression. To get insights into both conserved and species-specific variations during early limb patterning and outgrowth, we leverage genome-wide comprehensive assessment of chromatin accessibility and transcriptional changes during mouse forelimb and chicken wing bud development. Our analysis reveals temporal modulation of chromatin accessibility and expression as well as their temporal relationship during the progression of mouse forelimb and chicken wing bud development. Transcription factor binding site enrichment analysis and putative TF occupancy as inferred by integrating TF binding motifs and chromatin accessibility information reveal temporal TF-DNA interactions during forelimb/wing bud patterning. Finally, the integration of accessibility, expression, and TF binding site information allowed to identify candidate gene targets of HAND2 and GLI3 that include conserved as well as species-specific transcriptional regulator-gene interactions.
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Project description:In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis-regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis-regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis-regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development. Mouse 2-cell embryos were obtained from crosses of C57BL/6N x PWK for ChIP-seq samples.
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Project description:Single cell multiomics from 2 donor controls, expression and chromatin accessibility. Samples belong to gray matter tissue from the brain.
| EGAD00001008457 | EGA