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Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated microRNA Circuits

GSE42701 Homo sapiens Expression profiling by high throughput sequencing 7 samples Submitted 2013/01/17 Platform GPL9115Platform GPL11154
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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Also filed as BioProject PRJNA182938 and SRA study SRP017411. Searching any of these in the dataset finder brings you back here.

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