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Stem Cell Reports. 2019 Feb 12;12(2):191-200. doi: 10.1016/j.stemcr.2018.12.014. Epub 2019 Jan 17.

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

Author information

1
Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK. Electronic address: noakesz@cardiff.ac.uk.
2
Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
3
Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK.
4
School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
5
Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK. Electronic address: lim26@cardiff.ac.uk.

Abstract

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.

KEYWORDS:

Huntington's disease; caudal ganglionic eminence; cell replacement therapy; differentiation; human pluripotent stem cells; medial ganglionic eminence; striatal development; striatal interneurons

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