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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.

Pubmed ID: 20107439

Authors

  • Vierbuchen T
  • Ostermeier A
  • Pang ZP
  • Kokubu Y
  • S├╝dhof TC
  • Wernig M

Journal

Nature

Publication Data

February 25, 2010

Associated Grants

  • Agency: PHS HHS, Id: 1018438-142-PABCA
  • Agency: NINDS NIH HHS, Id: 5T32NS007280
  • Agency: NCI NIH HHS, Id: T32 CA009302
  • Agency: NHLBI NIH HHS, Id: U01 HL100397
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Action Potentials
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Markers
  • Cell Line
  • Cell Lineage
  • Cell Transdifferentiation
  • Cells, Cultured
  • Embryo, Mammalian
  • Fibroblasts
  • Mice
  • Nerve Tissue Proteins
  • Neurons
  • POU Domain Factors
  • Regenerative Medicine
  • Synapses
  • Tail
  • Time Factors
  • Transcription Factors