Direct conversion of fibroblasts to functional neurons by defined factors

Thomas Vierbuchen, Austin Ostermeier, Zhiping P. Pang, Yuko Kokubu, Thomas C. Südhof and Marius Wernig ()
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Thomas Vierbuchen: Institute for Stem Cell Biology and Regenerative Medicine
Austin Ostermeier: Institute for Stem Cell Biology and Regenerative Medicine
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,
Marius Wernig: Institute for Stem Cell Biology and Regenerative Medicine

Nature, 2010, vol. 463, issue 7284, 1035-1041

Abstract: 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.

Date: 2010
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DOI: 10.1038/nature08797

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