GSE118307 Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis [Timecourse RNA-Seq]

Contributors : Volker Busskamp ; Lisa K Kutsche ; Deisy M Gysi ; Mathias Lesche ; Andreas DahlSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensNon-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research