»Article,
Nature 2010,463.
»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 of19 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.