Detailed analysis of dorsal-ventral gradients of gene expression in the rat hippocampus
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ABSTRACT:
PROVIDER: PRJNA859286 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20272748.fastq.gz | Fastqsanger.gz | |||
| SRR20272749.fastq.gz | Fastqsanger.gz | |||
| SRR20272750.fastq.gz | Fastqsanger.gz | |||
| SRR20272751.fastq.gz | Fastqsanger.gz | |||
| SRR20272752.fastq.gz | Fastqsanger.gz |
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Project description:Dorsal and ventral parts of the hippocampus despite similar histological structure are known to be involved in performance of different functions. Previous studies using next generation sequencing showed that these two hippocampal parts differ in the expression of many genes, however, stability of dorsoventral gradient of gene expression remains open question. Here, we analyzed differential expression of genes between the dorsal and ventral hippocampus of rats in polyA-enriched samples and samples subjected to depletion of ribosomal RNA. We present here a detailed analysis of differentially expressed genes between the dorsal and ventral parts of the hippocampus. Intersection of our dataset with data of previous RNAseq studies revealed 544 genes are stably differentially expressed between the hippocampal parts suggesting that, despite strongly variability between the animals and sequencing approaches, there is a subset of genes whose expression stably differs between the dorsal and ventral hippocampus. Analysis of differential splicing showed that the dorsal and ventral parts of the hippocampus express 64 genes whose splice isoforms are different between the hippocampal parts. Furthermore, we show that depletion of ribosomal RNA increases representation of transposable elements in the RNAseq libraries and helps to detect a weak predominance of expression of these elements in the ventral hippocampus.
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Project description:The hippocampus - one of the most studied brain regions – is a key target of the stress response and vulnerable to the detrimental effects of stress. Although its intrinsic organization is highly conserved throughout its long dorsal-ventral axis, the dorsal hippocampus is linked to spatial navigation and memory formation, whereas the ventral hippocampus is linked to emotional regulation. Here, we provide the first combined transcriptomic and proteomic profiling that reveals striking differences between dorsal and ventral hippocampus. Using various acute stress challenges we demonstrate that both regions display very distinct molecular responses, and that the ventral hippocampus is particularly responsive to the effects of stress. We demonstrate that separately analyzing dorsal and ventral hippocampus greatly increases the ability to detect region-specific stress effects, and we identify an epigenetic network, which is specifically sensitive to acute stress in the ventral hippocampus.
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Project description:Purpose: The goal of this study was to characterize molecular stress responses on transcriptional level in dorsal and ventral hippocampus separately. Methods: mRNA profiles of whole, dorsal and ventral hippocampus of mice 45min after first exposure to different acute stressors. The stressors were novelty (6min novel environment), restraint (30min immobilization), or cold swim (6min in 18 degree Celcius water). 5 mice were used per condition, using Illumina HiSeq4000. The sequence reads that passed quality filters were mapped with STAR, counted with RSEM and differential gene expression was calculated using the bioconducter package edgeR. Results: With our workflow, we identified 13902 genes per sample. Approximately 20% of the genes were differentially expressed between dorsal and ventral hippocampus at baseline, with a log2 fold change >±0.3 and p value <0.005. Approximately 100 genes are differentially expressed upon stress treatment in the whole hippocampus. If ventral and dorsal hippocampus were analyzed separately, numbers increased to 150 and 250 respectively. Stress-responsive genes vary between dorsal and ventral hippocampus, and also vary between different stressors. Further analysis identified a functional epigenetic gene cluster specific for the stress response in the ventral hippocampus. Conclusions: Our study represents the first RNA-seq analysis of dorsal and ventral hippocampus after different acute stress exposures.
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Project description:We performed RNA sequencing of the dorsal and ventral parts of the hippocampus and compared it with previously published data to determine the differences in the dorsoventral gradients of gene expression that may result from biological or technical variability. Our data suggest that the dorsal and ventral parts of the hippocampus differ in the expression of genes related to signaling pathways mediated by classical neurotransmitters (glutamate, GABA, monoamines, etc.) as well as peptide and Wnt ligands. These hippocampal parts also diverge in the expression of axon-guiding molecules (both receptors and ligands) and splice isoforms of genes associated with intercellular signaling and cell adhesion. Furthermore, analysis of differential expressions of genes specific for astrocytes, microglia, oligodendrocytes, and vascular cells suggests that non-neuronal cells may also differ in the characteristics between hippocampal parts. Analysis of expression of transposable elements showed that depletion of ribosomal RNA strongly increased the representation of transposable elements in the RNA libraries and helped to detect a weak predominance of expression of these elements in the ventral hippocampus. Our data revealed new molecular dimensions of functional differences between the dorsal and ventral hippocampus and points to possible cascades that may be involved in the longitudinal organization of the hippocampus.
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Project description:During embryogenesis, the pancreas develops from separate dorsal and ventral buds, which fuse to form the mature pancreas. Little is known about the functional differences between these two buds or the relative contribution of cells derived from each portion to the pancreas after fusion. To follow the fate of dorsal or ventral bud derived cells in the pancreas after fusion, we produced chimeric Elas-GFP transgenic/wild type embryos in which either dorsal or ventral pancreatic bud cells expressed GFP. We found that ventral pancreatic cells migrate extensively into the dorsal pancreas after fusion, whereas the converse does not occur. Moreover, we found that annular pancreatic tissue is composed exclusively of ventral pancreas derived cells. To identify ventral pancreas specific genes that may play a role in pancreatic bud fusion, we isolated individual dorsal and ventral pancreatic buds, prior to fusion, from stage 38/39 Xenopus laevis tadpoles and compared their gene expression profiles. Morpholino-mediated knockdown of one of these ventral specific genes, transmembrane 4 superfamily member 3 (tm4sf3), inhibited dorsal-ventral pancreatic bud fusion as well as acinar cell differentiation. Conversely, overexpression of tm4sf3 promoted the development of annular pancreas. Our results are the first to define molecular and behavioral differences between the dorsal and ventral pancreas, and suggest an unexpected role for the ventral pancreas in pancreatic bud fusion. Experiment Overall Design: We analyzed two samples of dorsal and two samples of ventral pancreatic buds.
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