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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 15, 2022 |
| Title |
Systematic exploration of dynamic splicing networks reveals conserved multi-stage regulators of neurogenesis [RNAseq_Puf60] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Alternative splicing (AS) is a critical regulatory layer, yet factors controlling networks of functionally coordinated splicing events during developmental transitions remain poorly understood. Here, we employ a multifaceted screening strategy to define factors that control dynamically regulated splicing events associated with neurogenesis. Among numerous previously unknown regulators, Rbm38 acts widely to negatively impact neural AS through Ptbp1-dependent and -independent mechanisms. Puf60, a ubiquitous splicing factor, is surprisingly found to promote neural splicing patterns. This activity is determined by a vertebrate-conserved, neural-differential exon that remodels Puf60 co-factor interactions. Ablation of this exon rewires distinct AS networks in embryonic stem cells and at multiple stages of neural differentiation. Single-cell transcriptome analyses further reveal critical, multi-stage roles for Rbm38 and Puf60 isoforms in establishing neuronal identity. Our results thus reveal key new regulators of neurogenesis and establish how a single exon in a widely expressed splicing factor orchestrates temporal control over cell differentiation.
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| Overall design |
RNA-seq of N2A mouse neural cells upon control or Puf60 knockdown, the latter with or without rescue by knockdown-resistant Puf60 either with or without exon 5, in biological duplicate
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| Contributor(s) |
Han H, Best A, Braunschweig U, Mikolajewicz N, Li J, Roth J, Chowdhury F, Mantica F, Nabeel-Shah S, Parada G, Brown K, O'Hanlon D, Wei J, Yao Y, Zid AA, Comsa E, Jen M, Wang J, Datti A, Gonatopoulos-Pournatzis T, Weatheritt RJ, Greenblatt JF, L.Wrana J, Irimia M, Gingras A, Moffat J, Blencowe BJ |
| Citation(s) |
35914530 |
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| Submission date |
Oct 22, 2021 |
| Last update date |
Oct 14, 2022 |
| Contact name |
Ulrich Braunschweig |
| Organization name |
University of Toronto
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| Department |
Donnelly Centre
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| Lab |
Benjamin J. Blencowe
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| Street address |
160 College Street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5S 3E1 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE186389 |
Systematic exploration of dynamic splicing networks reveals conserved multi-stage regulators of neurogenesis |
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| Relations |
| BioProject |
PRJNA773724 |
| SRA |
SRP342713 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE186387_AltSplicing_Puf60.tab.gz |
5.4 Mb |
(ftp)(http) |
TAB |
| GSE186387_Expression_Puf60.tab.gz |
1.9 Mb |
(ftp)(http) |
TAB |
| GSE186387_vast-tools.AltSplicing_Puf60.tab.gz |
35.7 Mb |
(ftp)(http) |
TAB |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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