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Alternative RNA Splicing Associated With Mammalian Neuronal Differentiation

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TLDR
Describing the global differences of AS events between the 2 cell types by deep sequencing revealed cell type-specific AS in NPCs and neurons that are important for distinct functions pertinent to the corresponding cell type.
Abstract
Alternative pre-mRNA splicing (AS) produces multiple isoforms of mRNAs and proteins from a single gene. It is most prevalent in the mammalian brain and is thought to contribute to the formation and/or maintenance of functional complexity of the brain. Increasing evidence has documented the significant changes of AS between different regions or different developmental stages of the brain, however, the dynamics of AS and the possible function of it during neural progenitor cell (NPC) differentiation is less well known. Here, using purified NPCs and their progeny neurons isolated from the embryonic mouse cerebral cortex, we characterized the global differences of AS events between the 2 cell types by deep sequencing. The sequencing results revealed cell type-specific AS in NPCs and neurons that are important for distinct functions pertinent to the corresponding cell type. Our data may serve as a resource useful for further understanding how AS contributes to molecular regulations in NPCs and neurons during cortical development.

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Journal ArticleDOI

Coverage-dependent bias creates the appearance of binary splicing in single cells.

TL;DR: It is shown that accounting for the true amount of information recovered can produce biologically meaningful measurements of splicing in single cells, and that low gene expression and low capture efficiency distort the observed distribution of isoforms.
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Coverage-dependent bias creates the appearance of binary splicing in single cells

TL;DR: This work analyzed single cell alternative splicing in human and mouse single cell RNA-seq datasets, and modeled them with a probablistic simulator, and showed that accounting for the true amount of information recovered can produce biologically meaningful measurements ofsplicing in single cells.
Journal ArticleDOI

Thyroid hormone, gene expression, and Central Nervous System: Where we are.

TL;DR: It is concluded that TH, more precisely T3, acts mainly throughout its nuclear receptors, and that the deficiency of this hormone may cause mild (dysregulated mood in adulthood) to severe neurological impairment (Allan-Herndon-Dudley syndrome, presented as early as childhood).
Journal ArticleDOI

STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells

TL;DR: Global mapping of STRAP-RNA binding in mouse embryos by enhanced-CLIP sequencing reveals that STRAP preferably targets transcripts for nervous system development and regulates AS through preferred binding positions, as demonstrated for two neuronal-specific genes, Nnat and Mark3.
Journal ArticleDOI

Rhythmic Behavior Is Controlled by the SRm160 Splicing Factor in Drosophila melanogaster.

TL;DR: It is shown that SRm160 affects gene expression in pacemaker neurons of the Drosophila brain to ensure proper oscillations of the molecular clock and highlights the significant effect of alternative splicing on the nervous system and particularly on brain function in an in vivo model.
References
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Journal ArticleDOI

Pre-mRNA splicing and human disease

TL;DR: The purpose of this review is to highlight the different mechanisms by which disruption of pre-mRNA splicing play a role in human disease.
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Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis

TL;DR: The transcriptional landscapes of prefrontal cortex and perisylvian speech and language areas are characterized, which exhibit a population-level global expression symmetry and it is shown that differentially expressed genes are more frequently associated with human-specific evolution of putative cis-regulatory elements.
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Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases

TL;DR: Evidence indicates there is an optimal level of NRG/ ERBB signaling in the brain and deviation from it impairs brain functions, and NRGs/ERBBs and downstream signaling pathways may provide therapeutic targets for specific neuropsychiatric symptoms.
Journal ArticleDOI

Dynamics of 5-Hydroxymethylcytosine and Chromatin Marks in Mammalian Neurogenesis

TL;DR: Analysis of patterns of 5mC and 5hmC during neurogenesis in the embryonic mouse brain suggests that formation of 5HMC and loss of H3K27me3 cooperate to promote brain development, suggesting that5hmC is a stable epigenetic mark.
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