An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum

Abstract The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it ha...

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Autores principales:	Gustavo A. Higuera, Grazia Iaffaldano, Meiwand Bedar, Guy Shpak, Robin Broersen, Shashini T. Munshi, Catherine Dupont, Joost Gribnau, Femke M. S. de Vrij, Steven A. Kushner, Chris I. De Zeeuw
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86d10d54ca4343e8a9ee5b3e195133a2
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spelling	oai:doaj.org-article:86d10d54ca4343e8a9ee5b3e195133a22021-12-02T15:05:17ZAn expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum10.1038/s41598-017-09348-12045-2322https://doaj.org/article/86d10d54ca4343e8a9ee5b3e195133a22017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09348-1https://doaj.org/toc/2045-2322Abstract The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not been possible to efficiently generate Purkinje neuron (PN) progenitors from human or mouse pluripotent stem cells, let alone to develop a methodology for in vivo transplantation in the adult cerebellum. Here, we present a protocol to obtain an expandable population of cerebellar neuron progenitors from mouse embryonic stem cells. Our protocol is characterized by applying factors that promote proliferation of cerebellar progenitors. Cerebellar progenitors isolated in culture from cell aggregates contained a stable subpopulation of PN progenitors that could be expanded for up to 6 passages. When transplanted into the adult cerebellum of either wild-type mice or a strain lacking Purkinje cells (L7cre-ERCC1 knockout), GFP-labeled progenitors differentiated in vivo to establish a population of calbindin-positive cells in the molecular layer with dendritic trees typical of mature PNs. We conclude that this protocol may be useful for the generation and maturation of PNs, highlighting the potential for development of a regenerative medicine approach to the treatment of cerebellar neurodegenerative diseases.Gustavo A. HigueraGrazia IaffaldanoMeiwand BedarGuy ShpakRobin BroersenShashini T. MunshiCatherine DupontJoost GribnauFemke M. S. de VrijSteven A. KushnerChris I. De ZeeuwNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-19 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gustavo A. Higuera Grazia Iaffaldano Meiwand Bedar Guy Shpak Robin Broersen Shashini T. Munshi Catherine Dupont Joost Gribnau Femke M. S. de Vrij Steven A. Kushner Chris I. De Zeeuw An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
description	Abstract The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not been possible to efficiently generate Purkinje neuron (PN) progenitors from human or mouse pluripotent stem cells, let alone to develop a methodology for in vivo transplantation in the adult cerebellum. Here, we present a protocol to obtain an expandable population of cerebellar neuron progenitors from mouse embryonic stem cells. Our protocol is characterized by applying factors that promote proliferation of cerebellar progenitors. Cerebellar progenitors isolated in culture from cell aggregates contained a stable subpopulation of PN progenitors that could be expanded for up to 6 passages. When transplanted into the adult cerebellum of either wild-type mice or a strain lacking Purkinje cells (L7cre-ERCC1 knockout), GFP-labeled progenitors differentiated in vivo to establish a population of calbindin-positive cells in the molecular layer with dendritic trees typical of mature PNs. We conclude that this protocol may be useful for the generation and maturation of PNs, highlighting the potential for development of a regenerative medicine approach to the treatment of cerebellar neurodegenerative diseases.
format	article
author	Gustavo A. Higuera Grazia Iaffaldano Meiwand Bedar Guy Shpak Robin Broersen Shashini T. Munshi Catherine Dupont Joost Gribnau Femke M. S. de Vrij Steven A. Kushner Chris I. De Zeeuw
author_facet	Gustavo A. Higuera Grazia Iaffaldano Meiwand Bedar Guy Shpak Robin Broersen Shashini T. Munshi Catherine Dupont Joost Gribnau Femke M. S. de Vrij Steven A. Kushner Chris I. De Zeeuw
author_sort	Gustavo A. Higuera
title	An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
title_short	An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
title_full	An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
title_fullStr	An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
title_full_unstemmed	An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
title_sort	expandable embryonic stem cell-derived purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/86d10d54ca4343e8a9ee5b3e195133a2
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An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum

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