One-step induction of human GABAergic neurons promotes presynaptic development & synapse maturation.

ABSTRACT: Human induced pluripotent stem cells (iPSCs) present a powerful approach to study human brain physiology and disease, yet robust, pure GABAergic induction has remained difficult. Here we present improved, single-step, transposon-based GABAergic induction with Ascl1/Dlx2, which yields, unlike lentiviral approaches, exclusively GABAergic neurons and was validated across three independent iPSC lines. Co-seeding with Ngn2-induced excitatory neurons created stable networks of predefined excitation/inhibition ratios, with corresponding synapse ratios. Proteomic and electrophysiological characterization at different developmental time points showed that the single-step induced GABAergic neurons gain a proteomic profile that maps to different cortical interneuron subtypes and display typical GABAe

SUBMITTER: van Voorst TW 

PROVIDER: S-EPMC12265733 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature