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

Zoe Noakes; Francesca Keefe; Claudia Tamburini; Claire M. Kelly; Maria Cruz Santos; Stephen B. Dunnett; Adam C. Errington; Meng Li

doi:10.1016/j.stemcr.2018.12.014

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

Zoe Noakes^*, Francesca Keefe, Claudia Tamburini, Claire M. Kelly, Maria Cruz Santos, Stephen B. Dunnett, Adam C. Errington, Meng Li

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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.

Original language	English
Pages (from-to)	191-200
Number of pages	10
Journal	Stem Cell Reports
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/j.stemcr.2018.12.014
Publication status	Published - 12 Feb 2019
Externally published	Yes

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.stemcr.2018.12.014

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

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",

author = "Zoe Noakes and Francesca Keefe and Claudia Tamburini and Kelly, {Claire M.} and {Cruz Santos}, Maria and Dunnett, {Stephen B.} and Errington, {Adam C.} and Meng Li",

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doi = "10.1016/j.stemcr.2018.12.014",

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AU - Noakes, Zoe

AU - Keefe, Francesca

AU - Tamburini, Claudia

AU - Kelly, Claire M.

AU - Cruz Santos, Maria

AU - Dunnett, Stephen B.

AU - Errington, Adam C.

AU - Li, Meng

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N2 - 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.

AB - 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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KW - caudal ganglionic eminence

KW - cell replacement therapy

KW - differentiation

KW - human pluripotent stem cells

KW - medial ganglionic eminence

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KW - striatal interneurons

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

Abstract

Keywords

UN SDGs

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