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| Status |
Public on Mar 09, 2022 |
| Title |
Non-coding RNAs shape cortical neurons developmental trajectories |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A hallmark of cortical evolution is the high dynamic subventricular zone (SVZ) expansion, where basal progenitors (BPs) amplify and neuronal transcriptional programs unfold. How non-coding molecular factors such as microRNAs influence these developmental trajectories and regulate the acquisition of cortical type identities is largely unknown. Here we demonstrate that miR-137 and miR-122 regulate the positioning and identity features of superficial layer cortical neurons by acting at distinct steps of their developmental trajectories. MiR-137 sustains basal progenitor amplification by reverting their neurogenic commitment and inducing high proliferative state upregulating Cd63 and inhibiting Myt1l. Cd63 is an extra-cellular matrix (ECM) receptor which interacts with b3- and 1-integrin pathways to promote proliferation, while Myt1l is a transcription factor that promotes and sustains neuronal fate. The BPs amplification by miR-137 is converted in the promotion of intracortical projecting neuron (ICPN) identity and L2/3 expansion. As opposed to miR-137, miR-122 acts postmitotically, affecting the bioelectrical properties, the calcium and cytoskeleton dynamics of newborn neurons as well as their transcriptional program, leading to a persistent molecular immaturity across time. Overall, these findings reveal that miR-137 and miR-122 are key regulators of the developmental trajectory of cortical neurons across evolution.
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| Overall design |
Investigation of the non-coding RNAs miR-122 and miR-137 overexpression on progenitor and neuron transcriptional programs. psil-miR122, psil-miR137 or psil-scramble (control) plasmids were in utero electroporated together with pUB-GFP or pUB-Tomato plasmid in mouse embryos at embryonic day (E) 14.5, and cells collected at E15.5, E17.5 or postnatal day (P) 7 using fluorescence activated cell sorting (FACS). For comparison with layer 4 and layer 2/3 control cell molecular identities, pUB-GFP/Tomato plasmid was in utero electroporated at E14 and E15.5 respectively and cells collected at P3 and P7 using FACS. Collected cells were then processed for single-cell transcriptomics. psil-miR122 was in utero electroporated together with pUB-GFP plasmid in mouse embryos at E14.5; superficial and deep layers were microdissected at P7 and cells collected using FACS before being processed for bulk RNA sequencing.
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| Contributor(s) |
Tomasello U, Klingler E, Niquille M, Mule N, de Vevey L, Prados J, da Silva Santinha AJ, Borrell V, Dayer A, Jabudon D |
| Citation(s) |
35172154 |
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| Submission date |
Oct 19, 2020 |
| Last update date |
Mar 09, 2022 |
| Contact name |
Julien Prados |
| E-mail(s) |
julien.prados@unige.ch
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| Phone |
+41 22 37 95 396
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| Organization name |
University of Geneva
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| Department |
SCMU
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| Lab |
Bioinformatics Support Platform
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| Street address |
Rue Michel Servet 1
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| City |
Geneva |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (2524)
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| Relations |
| BioProject |
PRJNA669828 |
| SRA |
SRP287618 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159596_bulk_countmatrix.tsv.gz |
51.7 Kb |
(ftp)(http) |
TSV |
| GSE159596_singlecell_countmatrix.tsv.gz |
13.9 Mb |
(ftp)(http) |
TSV |
| GSE159596_singlecell_metadata.tsv.gz |
67.6 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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