Recent Advances of Brain Transcriptomics

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Neurogenomics".

Deadline for manuscript submissions: closed (25 June 2023) | Viewed by 3048

Special Issue Editors

Institute of Cytology and Genetics, 630090 Novosibirsk, Russia
Interests: brain transcriptiomics; alternative splicing; evolution of exon–intron structure; population genomics; next generation sequencing (NGS) methodologies
Special Issues, Collections and Topics in MDPI journals
Institute of Cytology and Genetics, 630090 Novosibirsk, Russia
Interests: RNA-Seq; brain transcriptomics; hypertension animal models; stress induced arterial hypertension; qTLs (quantitative trait loci); molecular mechanisms of hypertension; behavior
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advancements in RNA-seq technology in the last decade have underlined its power for elucidating the brain gene networks responsible for various stressful factors as well as pathologies such as Alzheimer’s and Parkinson’s in addition to other neurological diseases, including schizophrenia and depressive disorders. Single cell RNA-seq (scRNA-seq) allows for ascertaining the identities of various neurons and glia cells by elucidating the specific marker genes characterizing them. This technology underlines multiple novel stable cell colonies in the course of scRNA-seq analysis. Associative networks between cell colonies have been provided over the course of cell maturation, rendering an exhaustive picture of cell population development dynamics.

As a separate relevant issue, RNA-seq provides the basis for elucidation of cell/tissue-specific alternative splicing (AS) with high resolution. As is known, the brain maintains the most expanded AS-mediated proteome variability, as well as AS-mediated transcription regulation, via nonsense-mediated decay. The research of Barres lab reported a 10-fold expansion of transcript diversity when analyzing mouse brain transcriptomes (Yan et al., 2015). Currently, for neuronal identity, it is reported that the AS-specific profile is more specific and robust than gene expression in certain instances (Ha et al., 2021). Multiple databases such as ASCOT and Genome (for elucidating the tissue/cell-specific AS profiles for each gene) are arising, underlining the research of brain transcriptome structural and expression variability as a top priority.

Additionally, there is a genetic based vs. acquired trait paradigm, which would be represented by both genetic studies based on animal model strains/breeds (e.g., tame foxes, aggressive strains of rats, etc.) and those that acquired the trait within a single generation upon administering certain stress-related protocols.

In this Issue, we hope to address the spectra of physiological studies, including but not limited to animal models of social stress response and various brain disease related data/models using the abovementioned approaches and methods.

Dr. Vladimir Babenko
Dr. Olga Redina
Guest Editors

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Keywords

  • brain transcriptome
  • alternative splicing
  • molecular basis of neurological diseases
  • variability of brain proteome and plasticity
  • brain disease marker genes/networks
  • genetic basis of behavior
  • marker gene networks in various brain regions based on RNA-seq

Published Papers (2 papers)

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Research

35 pages, 9131 KiB  
Article
Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts
by Vladimir Babenko, Olga Redina, Dmitry Smagin, Irina Kovalenko, Anna Galyamina and Natalia Kudryavtseva
Genes 2023, 14(3), 599; https://doi.org/10.3390/genes14030599 - 27 Feb 2023
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Abstract
Both aggressive and aggression-deprived (AD) individuals represent pathological cases extensively studied in psychiatry and substance abuse disciplines. We employed the animal model of chronic social conflicts curated in our laboratory for over 30 years. In the study, we pursued the task of evaluation [...] Read more.
Both aggressive and aggression-deprived (AD) individuals represent pathological cases extensively studied in psychiatry and substance abuse disciplines. We employed the animal model of chronic social conflicts curated in our laboratory for over 30 years. In the study, we pursued the task of evaluation of the key events in the dorsal striatum transcriptomes of aggression-experienced mice and AD species, as compared with the controls, using RNA-seq profiling. We evaluated the alternative splicing-mediated transcriptome dynamics based on the RNA-seq data. We confined our attention to the exon skipping (ES) events as the major AS type for animals. We report the concurrent posttranscriptional and posttranslational regulation of the ES events observed in the phosphorylation cycles (in phosphoproteins and their targets) in the neuron-specific genes of the striatum. Strikingly, we found that major neurospecific splicing factors (Nova1, Ptbp1, 2, Mbnl1, 2, and Sam68) related to the alternative splicing regulation of cAMP genes (Darpp-32, Grin1, Ptpn5, Ppp3ca, Pde10a, Prkaca, Psd95, and Adora1) are upregulated specifically in aggressive individuals as compared with the controls and specifically AD animals, assuming intense switching between isoforms in the cAMP-mediated (de)phosphorylation signaling cascade. We found that the coding alternative splicing events were mostly attributed to synaptic plasticity and neural development-related proteins, while the nonsense-mediated decay-associated splicing events are mostly attributed to the mRNA processing of genes, including the spliceosome and splicing factors. In addition, considering the gene families, the transporter (Slc) gene family manifested most of the ES events. We found out that the major molecular systems employing AS for their plasticity are the ‘spliceosome’, ‘chromatin rearrangement complex’, ‘synapse’, and ‘neural development/axonogenesis’ GO categories. Finally, we state that approximately 35% of the exon skipping variants in gene coding regions manifest the noncoding variants subject to nonsense-mediated decay, employed as a homeostasis-mediated expression regulation layer and often associated with the corresponding gene expression alteration. Full article
(This article belongs to the Special Issue Recent Advances of Brain Transcriptomics)
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13 pages, 2498 KiB  
Article
Elevated ETV6 Expression in Glioma Promotes an Aggressive In Vitro Phenotype Associated with Shorter Patient Survival
by Zhang Xiong, Shuai Wu, Feng-jiao Li, Chen Luo, Qiu-yan Jin, Ian David Connolly, Melanie Hayden Gephart and Linya You
Genes 2022, 13(10), 1882; https://doi.org/10.3390/genes13101882 - 17 Oct 2022
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Abstract
Background: GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal [...] Read more.
Background: GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal mature astrocytes. We hypothesized that ETV6 played a role in GBM tumor progression. Methods: Expression of ETV6 was first examined in two American and three Chinese tissue microarrays. The correlation between ETV6 staining intensity and patient survival was calculated, followed by validation using public databases—TCGA and REMBRANDT. The effect of ETV6 knockdown on glioma cell proliferation (EdU), viability (AnnexinV labeling), clonogenic growth (colony formation), and migration/invasion (transwell assays) in GBM cells was tested. RNA sequencing and Western blot were performed to elucidate the underlying molecular mechanisms. Results: ETV6 was highly expressed in GBM and associated with an unfavorable prognosis. ETV6 silencing in glioma cells led to increased apoptosis or decreased proliferation, clonogenicity, migration, and invasion. RNA-Seq-based gene expression and pathway analyses revealed that ETV6 knockdown in U251 cells led to the upregulation of genes involved in extracellular matrix organization, NF-κB signaling, TNF-mediated signaling, and the downregulation of genes in the regulation of cell motility, cell proliferation, PI3K-AKT signaling, and the Ras pathway. The downregulation of the PI3K-AKT and Ras-MAPK pathways were further validated by immunoblotting. Conclusion: Our findings suggested that ETV6 was highly expressed in GBM and its high expression correlated with poor survival. ETV6 silencing decreased an aggressive in vitro phenotype probably via the PI3K-AKT and Ras-MAPK pathways. The study encourages further investigation of ETV6 as a potential therapeutic target of GBM. Full article
(This article belongs to the Special Issue Recent Advances of Brain Transcriptomics)
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