Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 16 (7), 1942-53

Direct Induction and Functional Maturation of Forebrain GABAergic Neurons From Human Pluripotent Stem Cells

Affiliations

Direct Induction and Functional Maturation of Forebrain GABAergic Neurons From Human Pluripotent Stem Cells

Alfred Xuyang Sun et al. Cell Rep.

Abstract

Gamma-aminobutyric acid (GABA)-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs) into GABAergic neurons (iGNs) with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6-8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs). Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons.

Keywords: GABA; direct conversion; human pluripotent stem cells; interneuron; synapse.

Similar articles

See all similar articles

Cited by 20 articles

See all "Cited by" articles

MeSH terms

LinkOut - more resources

Feedback