Human Pluripotent Stem Cell-Derived Striatal Interneurons: Differentiation and Maturation In Vitro and in the Rat Brain

Abstract

Summary: Striatal interneurons are born in the medial and caudal ganglionic eminences (MGE and CGE) and play an important role in human striatal function and dysfunction in Huntington's disease and dystonia. MGE/CGE-like neural progenitors have been generated from human pluripotent stem cells (hPSCs) for studying cortical interneuron development and cell therapy for epilepsy and other neurodevelopmental disorders. Here, we report the capacity of hPSC-derived MGE/CGE-like progenitors to differentiate into functional striatal interneurons. In vitro, these hPSC neuronal derivatives expressed cortical and striatal interneuron markers at the mRNA and protein level and displayed maturing electrophysiological properties. Following transplantation into neonatal rat striatum, progenitors differentiated into striatal interneuron subtypes and were consistently found in the nearby septum and hippocampus. These findings highlight the potential for hPSC-derived striatal interneurons as an invaluable tool in modeling striatal development and function in vitro or as a source of cells for regenerative medicine. : In this report, Noakes and colleagues highlight the importance of studying human striatal interneurons and demonstrate the presence of striatal interneuron markers in hPSCs differentiated toward MGE and CGE fate in vitro. HPSC-GABAergic neurons displayed functional intrinsic and network properties in vitro, and adopted striatal interneuron subtype fates in vivo, making them a suitable tool for further research. Keywords: human pluripotent stem cells, striatal interneurons, striatal development, medial ganglionic eminence, caudal ganglionic eminence, Huntington's disease, cell replacement therapy, differentiation