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Human Pluripotent Stem Cell-Derived Striatal Interneurons: Differentiation and Maturation In Vitro and in the Rat Brain
Author(s) -
Zoe Noakes,
Francesca Keefe,
Claudia Tamburini,
Claire M. Kelly,
Maria Cruz-Santos,
Stephen B. Dunnett,
Adam C. Errington,
Meng Li
Publication year - 2019
Publication title -
stem cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.207
H-Index - 76
ISSN - 2213-6711
DOI - 10.1016/j.stemcr.2018.12.014
Subject(s) - biology , induced pluripotent stem cell , neuroscience , interneuron , striatum , progenitor cell , medium spiny neuron , ganglionic eminence , transplantation , embryonic stem cell , stem cell , dystonia , neural stem cell , hippocampus , microbiology and biotechnology , dopamine , medicine , inhibitory postsynaptic potential , genetics , gene
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.

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