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Direct conversion of fibroblasts to functional neurons by defined factors

Author

Listed:
  • Thomas Vierbuchen

    (Institute for Stem Cell Biology and Regenerative Medicine
    Program in Cancer Biology,)

  • Austin Ostermeier

    (Institute for Stem Cell Biology and Regenerative Medicine
    Program in Cancer Biology,)

  • Zhiping P. Pang

    (Department of Molecular and Cellular Physiology,)

  • Yuko Kokubu

    (Institute for Stem Cell Biology and Regenerative Medicine)

  • Thomas C. Südhof

    (Department of Molecular and Cellular Physiology,
    Howard Hughes Medical Institute, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, California 94304, USA)

  • Marius Wernig

    (Institute for Stem Cell Biology and Regenerative Medicine
    Program in Cancer Biology,)

Abstract

Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.

Suggested Citation

  • Thomas Vierbuchen & Austin Ostermeier & Zhiping P. Pang & Yuko Kokubu & Thomas C. Südhof & Marius Wernig, 2010. "Direct conversion of fibroblasts to functional neurons by defined factors," Nature, Nature, vol. 463(7284), pages 1035-1041, February.
  • Handle: RePEc:nat:nature:v:463:y:2010:i:7284:d:10.1038_nature08797
    DOI: 10.1038/nature08797
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    Cited by:

    1. Anat Kreimer & Tal Ashuach & Fumitaka Inoue & Alex Khodaverdian & Chengyu Deng & Nir Yosef & Nadav Ahituv, 2022. "Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Emre Bektik & Adrienne Dennis & Prateek Prasanna & Anant Madabhushi & Ji-Dong Fu, 2017. "Single cell qPCR reveals that additional HAND2 and microRNA-1 facilitate the early reprogramming progress of seven-factor-induced human myocytes," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-16, August.
    3. Lining Liang & Hao Sun & Wei Zhang & Mengdan Zhang & Xiao Yang & Rui Kuang & Hui Zheng, 2016. "Meta-Analysis of EMT Datasets Reveals Different Types of EMT," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-22, June.
    4. David Lamparter & Daniel Marbach & Rico Rueedi & Sven Bergmann & Zoltán Kutalik, 2017. "Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility," PLOS Computational Biology, Public Library of Science, vol. 13(1), pages 1-19, January.

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