In the future, it will be important to explore whether transcription factor combinations can generate selective interneuron subtypes such as PV interneurons. Surprisingly, combining Ascl1 and Dlx2 with additional subtype-specific transcription factors did not result in different subclasses of GABAergic neurons (Supplementary Fig. 10). Consistently, simultaneous expression of Asc1, Dlx2, Lhx6 and miR-9/9*-124 was recently shown to induce a GABAergic cell population similar to that induced by only Ascl1 and Dlx231. This suggests that timing and cellular context are critical for productive engagement of some transcription factors to specify specific neuronal subtypes3. While there is a wealth of information about mouse GABAergic neurons such as molecular markers, morphology and electrophysiological properties, similar depth of information for primary human GABAergic neurons is only emerging. Better characterization of primary human neurons will greatly facilitate the interpretation of properties of neurons generated in vitro, such as the GABAergic AD-iN cells described in this paper.
