Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits
Open accessAbstract
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 polypyrimidine-tract-binding (PTB) protein, 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 derepressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in nonneuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage.
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Reduced PTBP1 expression enhances miR-124 repression of the REST complex.
“Reduced PTBP1 expression also enhances miR-124 repression of the REST (repressor element 1-silencing transcription factor) complex16”
From The neurogenetics of alternative splicing (2016) · cites this paper as [16]
Depletion of PTBP1 from cultured fibroblasts is sufficient to induce their trans-differentiation into neurons.
“the simple depletion of PTBP1 from cultured fibroblasts is sufficient to induce their trans-differentiation into neurons16.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [16]
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- Authors
- Xue, Y., Ouyang, K., Huang, J., Zhou, Y., Ouyang, H., Li, H., Wang, G., Wu, Q., Wei, C., Bi, Y., Jiang, L., Cai, Z., Sun, H., Zhang, K., Zhang, Y., Chen, J., & Fu, X.-D.
- Affiliations
- University of California San Diego (US)
- Wuhan University (CN)
- Corresponding author
- Fu, Xiang-Dong
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 152
- Issue
- 1-2
- Pages
- 82-96
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3552026
- OpenAlex
- W2019346039
- Cited by
- 562
- References
- 60
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 31 · 2023: 40 · 2022: 48 · 2021: 50 · 2020: 42 · 2019: 40 · 2018: 32 · 2017: 54 · 2016: 56 · 2015: 46 · 2014: 49 · 2013: 29
- FWCI
- 26.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Key Research and Development Program of China
- National Human Genome Research Institute (HG004659, R01HG004659)
- National Eye Institute (R01EY021374, EY021374)
- National Institute of General Medical Sciences (R01GM052872, GM049369, GM052872, R01GM049369)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-124, microRNA regulation, RNA-binding proteins, neuronal reprogramming, RNA secondary structure, microRNA target binding
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Fibroblasts, Humans, Neurons, RNA Splicing, Synapses, Down-Regulation, Cell Lineage, MicroRNAs, Polypyrimidine Tract-Binding Protein, Mice
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