The medium-sized spiny neurons, the main projection neurons of the striatum, are generated in the lateral ganglionic eminence (LGE) and degenerate in the early stages of Huntington's disease (HD) – for which no pharmacological treatment is yet available. Hence, an efficient way to derive striatal neurons is crucial for disease modelling, drug development and cell-replacement therapy. Striatal neurons have previously been generated from human pluripotent stem cell (hPSC)-derived neural progenitors treated with sonic hedgehog (SHH), or SHH plus Wnt pathway inhibition. Now, Meng Li and co-workers (p. 1375) report a more robust and efficient way to generate functional striatal neurons from hPSCs. They show that activin A induces LGE characteristics in hPSC-derived neural progenitors. This is independent of SHH but requires CTIP2, a transcription factor required for striatal neuron development. Furthermore, the activin-patterned neural precursors efficiently generate functional DARPP32+ GABAergic striatal neurons in vitro, and acquire striatal spiny neuron properties without overgrowth or teratoma formation upon engraftment in a rat HD model. Altogether, these findings uncover a novel role for activin A in striatal projection neuron specification and establish a robust protocol for deriving these neurons.
ActivinA-ting spiny neuron production from hPSCs
ActivinA-ting spiny neuron production from hPSCs. Development 1 April 2015; 142 (7): e0701. doi:
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