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| Status |
Public on Jun 27, 2018 |
| Title |
Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: 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 disorders (ASD), epilepsy and intellectual disability (ID). Yet, how miR-146a upregulation affects the developing fetal brain remains unclear.
Methods: 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.
Results: 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 ten percent 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.
Conclusion: Our results demonstrate the dynamic roles of miR-146a in early neuronal development and provide new insight into the molecular events that link miR146a overexpression to impaired neurodevelopment. This, in turn, may yield new therapeutic targets and strategies.
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| Overall design |
For each cell line, we used technical triplicates. The samples are matched based on passage number.
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| Contributor(s) |
Nguyen LS, Fregeac J, Bole-Feysot C, Cagnard N, Iyer A, Anink J, Aronica E, Alibeu O, Nitschke P, Colleaux L |
| Citation(s) |
29951184 |
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| Submission date |
Jun 29, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Lam Son Nguyen |
| E-mail(s) |
[email protected]
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| Organization name |
INSERM U1163
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| Department |
Institute Imagine
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| Street address |
24 Bld du Montparnasse
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| City |
Paris |
| State/province |
IDF |
| ZIP/Postal code |
75015 |
| Country |
France |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA392463 |
| SRA |
SRP110769 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE100670_H9_Processed_File.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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