Hester ME, Murtha MJ, Song S, Rao M, Miranda CJ, Meyer K, Tian J, Boulting G, Schaffer DV, Zhu MX, Pfaff SL, Gage FH, Kaspar BK.
Rapid and efficient generation of functional motor neurons from human pluripotent stem cells using gene delivered transcription factor codes.
Mol Ther. 2011 Oct;19(10):1905-12.
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This paper by Kaspar and colleagues aimed to accelerate the generation of motor neurons from induced pluripotent stem (iPS) cells.
Indeed, this is currently a bottleneck for all stem cell biologists interested in using iPS-derived motor neurons
for in-vitro disease modeling. Currently, iPS cells need to be differentiated in vitro for at least 42 days
in order to get functional motor neurons. This is a long time, especially if you want to use large numbers of these neurons
for drug screenings or high-throughput procedures.
Kaspar and colleagues conceived to accelerate cell differentiation by expressing a set of three transcription factors that are
critical to promote this neuronal lineage during development. Interestingly, their expression is sufficient to boost
neuronal differentiation in time and number, generating functional motor neurons in as few as 11 days.
The authors provided results for only this single combination of master genes, leaving open the possibility
to further increase the cell differentiating output with new combinations of related transcription factors.
This is a great advance that will likely speed up research on in-vitro modeling of motor neuron diseases. Importantly,
these results indicate that a similar approach is conceivable for a fast-track generation of other neuronal sub-types.
Thus, hopefully, new studies will follow the experimental strategy designed by these authors.