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Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders

Overview of attention for article published in Molecular Autism, June 2018
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Title
Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders
Published in
Molecular Autism, June 2018
DOI 10.1186/s13229-018-0219-3
Pubmed ID
Authors

Lam Son Nguyen, Julien Fregeac, Christine Bole-Feysot, Nicolas Cagnard, Anand Iyer, Jasper Anink, Eleonora Aronica, Olivier Alibeu, Patrick Nitschke, Laurence Colleaux

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs have emerged as important modulators of brain development and neuronal function and are implicated in several neurological diseases. Previous studies found miR-146a upregulation is the most common miRNA deregulation event in neurodevelopmental disorders such as autism spectrum disorder (ASD), epilepsy, and intellectual disability (ID). Yet, how miR-146a upregulation affects the developing fetal brain remains unclear. We analyzed the expression of miR-146a in the temporal lobe of ASD children using Taqman assay. To assess the role of miR-146a in early brain development, we generated and characterized stably induced H9 human neural stem cell (H9 hNSC) overexpressing miR-146a using various cell and molecular biology techniques. We first showed that miR-146a upregulation occurs early during childhood in the ASD brain. In H9 hNSC, miR-146a overexpression enhances neurite outgrowth and branching and favors differentiation into neuronal like cells. Expression analyses revealed that 10% of the transcriptome was deregulated and organized into two modules critical for cell cycle control and neuronal differentiation. Twenty known or predicted targets of miR-146a were significantly deregulated in the modules, acting as potential drivers. The two modules also display distinct transcription profiles during human brain development, affecting regions relevant for ASD including the neocortex, amygdala, and hippocampus. Cell type analyses indicate markers for pyramidal, and interneurons are highly enriched in the deregulated gene list. Up to 40% of known markers of newly defined neuronal lineages were deregulated, suggesting that miR-146a could participate also in the acquisition of neuronal identities. Our results demonstrate the dynamic roles of miR-146a in early neuronal development and provide new insight into the molecular events that link miR-146a overexpression to impaired neurodevelopment. This, in turn, may yield new therapeutic targets and strategies.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 8 38%
Student > Master 5 24%
Researcher 4 19%
Student > Ph. D. Student 2 10%
Student > Doctoral Student 1 5%
Other 1 5%
Readers by discipline Count As %
Unspecified 9 43%
Neuroscience 5 24%
Biochemistry, Genetics and Molecular Biology 3 14%
Agricultural and Biological Sciences 2 10%
Computer Science 1 5%
Other 1 5%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 June 2018.
All research outputs
#11,685,420
of 13,157,264 outputs
Outputs from Molecular Autism
#407
of 418 outputs
Outputs of similar age
#233,426
of 268,692 outputs
Outputs of similar age from Molecular Autism
#2
of 2 outputs
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So far Altmetric has tracked 418 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 30.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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