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Human pluripotent stem cell-derived striatal interneurons: differentiation and maturation in vitro and in the rat brain

Noakes, Zoe, Keefe, Francesca, Tamburini, Claudia, Kelly, Claire M., Cruz Santos, Maria, Dunnett, Stephen B., Errington, Adam C. and Li, Meng 2019. Human pluripotent stem cell-derived striatal interneurons: differentiation and maturation in vitro and in the rat brain. Stem Cell Reports 12 (2) , pp. 191-200. 10.1016/j.stemcr.2018.12.014

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Biosciences
Publisher: Elsevier
ISSN: 2213-6711
Date of First Compliant Deposit: 18 February 2019
Date of Acceptance: 18 December 2018
Last Modified: 05 Apr 2019 15:33
URI: http://orca.cf.ac.uk/id/eprint/119674

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