Robust Production of Parvalbumin Interneurons and Fast-Spiking Neurons from Human Medial Ganglionic Eminence Organoids.

ABSTRACT: The medial ganglionic eminence (MGE) gives rise to parvalbumin (PV)- and somatostatin (SST)-expressing cortical interneurons essential for regulating cortical excitability. Although PV interneurons are linked to various neurodevelopmental and neurodegenerative disorders, reliably generating them from human pluripotent stem cells (hPSCs) has been extremely challenging. We present a robust, reproducible protocol for generating single-rosette MGE organoids (MGEOs) from hPSCs. Transcriptomic analyses reveal that MGEOs exhibit MGE regional identity and faithfully model the developing human fetal MGE. As MGEOs mature, they generate abundant PV-expressing cortical interneurons, including putative basket and axoaxonic cells, at a scale not previously achieved in vitro. When fused with hPSC-

SUBMITTER: Varela MC 

PROVIDER: S-EPMC12236662 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature