Abstract
Integrating differential RNA and miRNA expression during neuronal lineage induction of human embryonic stem cells we identified miR-934, a primate-specific miRNA that displays a stage-specific expression pattern during progenitor expansion and early neuron generation. We demonstrate the biological relevance of this finding by comparison with data from early to mid-gestation human cortical tissue. Further we find that miR-934 directly controls progenitor to neuroblast transition and impacts on neurite growth of newborn neurons. In agreement, miR-934 targets are involved in progenitor proliferation and neuronal differentiation whilst miR-934 inhibition results in profound global transcriptome changes associated with neurogenesis, axonogenesis, neuronal migration and neurotransmission. Interestingly, miR-934 inhibition affects the expression of genes associated with the subplate zone, a transient compartment most prominent in primates that emerges during early corticogenesis. Our data suggest that mir-934 is a novel regulator of early human neurogenesis with potential implications for a species-specific evolutionary role in brain function.
Keywords:
PAX6; developmental biology; doublecortin; early neurons; human; neural induction; neuritogenesis; progenitor cell.
© 2020, Prodromidou et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Doublecortin Domain Proteins
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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Human Embryonic Stem Cells / physiology
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Humans
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Male
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MicroRNAs / physiology*
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Microtubule-Associated Proteins / metabolism
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Neural Stem Cells / physiology*
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Neurogenesis / genetics*
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Neuropeptides / metabolism
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PAX6 Transcription Factor / metabolism
Substances
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Doublecortin Domain Proteins
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MIRN934 microRNA, human
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MicroRNAs
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Microtubule-Associated Proteins
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Neuropeptides
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PAX6 Transcription Factor
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PAX6 protein, human
Associated data
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GEO/GSE101548
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GEO/GSE119760
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SRA/SRR1636969
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SRA/SRR1636968
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SRA/SRR1636959
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SRA/SRR1636960
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SRA/SRR1636962
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SRA/SRR1636963
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SRA/SRR1636965
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SRA/SRR1988287
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SRA/SRR1988288
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SRA/SRR1988291
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SRA/SRR1988292
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SRA/SRR1658346
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SRA/SRR1658360
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SRA/SRR1759212
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SRA/SRR1759213
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SRA/SRR2061800
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SRA/SRR2061801
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SRA/SRR2061795
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SRA/SRR2061797
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SRA/SRR2061803
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SRA/SRR2061804
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SRA/SRR2061810
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SRA/SRR828708
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SRA/SRR828709
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SRA/SRR531688
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SRA/SRR531687
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SRA/SRR531692
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SRA/SRR531694
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SRA/SRR531683
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SRA/SRR531684
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SRA/SRR1949839
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SRA/SRR1949841
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SRA/SRR1949847
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SRA/SRR1949850
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SRA/SRR1949858
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SRA/SRR1949861
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SRA/(SRA) SRR1820679
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SRA/SRR1820680
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SRA/SRR2174513
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SRA/SRR2174514
-
SRA/SRR2174515
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SRA/SRR2174516
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SRA/SRR2174517
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SRA/SRR2174518
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SRA/SRR2174519
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SRA/SRR2174520
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SRA/SRR2174537
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SRA/SRR2174538
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SRA/SRR2174541
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SRA/SRR2174542
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SRA/SRR191548
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SRA/SRR191578
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SRA/SRR070232
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SRA/SRR070230
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SRA/SRR6328631
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SRA/SRR6328627
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SRA/SRR6328628
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SRA/SRR6328630
Grants and funding
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.