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| Status |
Public on Jan 17, 2013 |
| Title |
Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated microRNA Circuits |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell lineage-specific transcription factors. Here we report that repression of a single RNA binding protein PTB, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-differentiation of fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we show that PTB has a previously undocumented function in the regulation of microRNA functions, suppressing or enhancing microRNA targeting by competitive binding on target mRNA or altering local RNA secondary structure. A key event during neuronal induction is the relief of PTB-mediated blockage of microRNA action on multiple components of the REST complex, thereby de-repressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in non-neuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage.
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| Overall design |
Examination of PTB regulated AGO2/microRNA targeting in Hela cells by CLIP-seq (two biological replicates) , paired-end RNA-seq (control and PTB knockdown) and 3’end stability RNA-seq (control and PTB knockdown)
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| Contributor(s) |
Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H, Wang G, Wu Q, Wei C, Bi Y, Jiang L, Cai Z, Sun H, Zhang K, Zhang Y, Chen J, Fu X |
| Citation(s) |
23313552 |
| Submission date |
Dec 03, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Jie Huang |
| E-mail(s) |
jih052@ucsd.edu
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| Phone |
8588882373
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| Fax |
858-822-6920
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| Organization name |
UC San Diego
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| Department |
Department of Cellular and Molecular Medicine
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| Lab |
George Palade Laboratories
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| Street address |
9500 Gilman Drive, Room 231
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| City |
La Jolla, San Diego |
| State/province |
CA |
| ZIP/Postal code |
92093-0651 |
| Country |
USA |
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| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA182938 |
| SRA |
SRP017411 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE42701_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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