Direct conversion of fibroblasts to functional neurons by defined factors

Direct conversion of fibroblasts to functional neurons by defined factors 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Nature Publishing Group (NPG)

Direct conversion of fibroblasts to functional neurons by defined factors

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Publisher
Nature Publishing Group (NPG)
Copyright
Copyright © 2010 Macmillan Publishers Limited. All rights reserved
ISSN
0028-0836
eISSN
1476-4687
D.O.I.
10.1038/nature08797
Publisher site
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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.

Journal

NatureNature Publishing Group (NPG)

Published: Jan 27, 2010

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