Cited by 562Pluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanismsMicroRNA in disease regulation

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

Open access
Xue, Yuanchao, Ouyang, Kunfu, Huang, Jie, Zhou, Yu, Ouyang, Hong, Li, Hairi, Wang, Gang, Wu, Qijia +9 more·2013·Cell

Abstract

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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Crossref · 10.1016/j.cell.2012.11.045

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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
Venue
Cell
Publisher
Elsevier BV
Published
2013-01
Volume
152
Issue
1-2
Pages
82-96
ISSN
0092-8674 (ISSN-L)
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
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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