Several groups have reported stepwise maturation of GABAergic interneurons through a PSC-derived MGE-like intermediate1,2,4. Remarkably, transient expression of AD is sufficient to generate a panel of GABAergic neurons that are surprisingly similar to those matured from MGE-like cells, but AD expression requires much less time. Some functional properties of 7-week AD-iN cells (e.g., input resistance and resting membrane potential) were strikingly similar to those of MGE-like cells 10 weeks after differentiation (i.e.,15 weeks after PSC differentiation). Meanwhile, the peak voltage-gated Na+ and K+ channel currents and membrane capacitance of AD-iN cells were more comparable to those of progenitor-derived interneurons at 25 weeks after differentiation2. Apparently, the transcription factors induce not only specification but also an accelerated maturation program. It is worth noting that when human MGE-like cells were cocultured with mouse embryonic cortical neurons, prominent inhibitory synaptogenesis could be detected after ~4 weeks1, suggesting the feasibility of enhanced maturation of human MGE-like cell in vitro.
