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| Status |
Public on Jun 26, 2013 |
| Title |
Muscleblind-like proteins regulate embryonic stem cell-specific alternative splicing and reprogramming I |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Previous investigations of the core gene regulatory circuitry that controls embryonic stem cell (ESC) pluripotency have largely focused on the roles of transcription, chromatin and non- coding RNA regulators. Alternative splicing (AS) represents a widely acting mode of gene regulation, yet its role in the regulation of ESC pluripotency and differentiation is poorly understood. Here, we identify the Muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of AS events that are differentially regulated between ESCs and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ESC-like AS pattern for at least half of these AS events. Among the events is an ESC-specific AS switch in the forkhead family transcription factor FOXP1 that controls pluripotency. Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells (iPSCs) during somatic cell reprogramming.
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| Overall design |
mRNA profiles of various embryonic stem cells, tissues and cell lines from human and mouse using high-throughput sequencing data and the role of MBNL proteins in regulation of ESC-differential alternative splicing
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| Contributor(s) |
Liu Y, Han H, Irimia M, Blencowe BJ, Wrana JL |
| Citation(s) |
23739326 |
| Submission date |
Mar 26, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Manuel Irimia |
| E-mail(s) |
mirimia@gmail.com
|
| Phone |
+34933160212
|
| Organization name |
Centre for Genomic Regulation
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| Department |
Systems Biology Unit
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| Street address |
88 Dr. Aiguader
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| City |
Barcelona |
| State/province |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE45505 |
Muscleblind-like proteins regulate embryonic stem cell-specific alternative splicing and reprogramming |
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| Relations |
| SRA |
SRP019988 |
| BioProject |
PRJNA195385 |
