Human Pluripotent Stem Cell-Derived Striatal Interneurons: Differentiation and Maturation In Vitro and in the Rat Brain
Maria, Cruz Santos
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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.
Stem Cell Reports;
Noakes, Z., Keefe, F., Tamburini, C., Kelly, C.M., Santos, M.C., Dunnett, S.B., Errington, A.C. and Li, M. (2019) ‘Human pluripotent stem cell-derived striatal interneurons: differentiation and maturation in vitro and in the rat brain’, Stem Cell Reports. DOI: 10.1016/j.stemcr.2018.12.014.
Dynodwr Gwrthrych Digidol (DOI)https://doi.org/10.1016/j.stemcr.2018.12.014
Article published in Stem Cell Reports on 17 January 2019 (online), available open access at: https://doi.org/10.1016/j.stemcr.2018.12.014.
This work was supported by the UK Medical Research Council.
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Arber, Charles; Precious, Sophie; Cambray, Serafi; Risner-Janiczek, Jessica; Kelly, Claire; Noakes, Zoe; Fjodorova, Marija; Heuer, Andreas; Ungless, Mark; Rodriguez, Tristan; Rosser, Anne; Dunnett, Stephen; Li, Meng (The Company of Biologists, 2015-04-01)The efficient generation of striatal neurons from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) is fundamental for realising their promise in disease modelling, pharmaceutical drug screening ...
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