Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential

Abstract Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA...

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Autores principales:	Stefania Fedele, Ginetta Collo, Katharina Behr, Josef Bischofberger, Stephan Müller, Tilo Kunath, Klaus Christensen, Anna Lisa Gündner, Martin Graf, Ravi Jagasia, Verdon Taylor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ed1c6e948cd4fae965b4783e0f2222b
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spelling	oai:doaj.org-article:5ed1c6e948cd4fae965b4783e0f2222b2021-12-02T16:07:44ZExpansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential10.1038/s41598-017-05633-12045-2322https://doaj.org/article/5ed1c6e948cd4fae965b4783e0f2222b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05633-1https://doaj.org/toc/2045-2322Abstract Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked. We demonstrate that expanded mFPPs have increased DA neuron potential and differentiate more efficiently and rapidly than progenitors generated by standard protocols. In addition, this novel method results in increased numbers of DA neurons that in vitro show characteristic electrophysiological properties of nigrostriatal DA neurons, produce high levels of dopamine, and integrate into host mice when grafted in vivo. Thus, we describe a robust method for producing human mesencephalic DA neurons from hiPSCs.Stefania FedeleGinetta ColloKatharina BehrJosef BischofbergerStephan MüllerTilo KunathKlaus ChristensenAnna Lisa GündnerMartin GrafRavi JagasiaVerdon TaylorNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefania Fedele Ginetta Collo Katharina Behr Josef Bischofberger Stephan Müller Tilo Kunath Klaus Christensen Anna Lisa Gündner Martin Graf Ravi Jagasia Verdon Taylor Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
description	Abstract Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked. We demonstrate that expanded mFPPs have increased DA neuron potential and differentiate more efficiently and rapidly than progenitors generated by standard protocols. In addition, this novel method results in increased numbers of DA neurons that in vitro show characteristic electrophysiological properties of nigrostriatal DA neurons, produce high levels of dopamine, and integrate into host mice when grafted in vivo. Thus, we describe a robust method for producing human mesencephalic DA neurons from hiPSCs.
format	article
author	Stefania Fedele Ginetta Collo Katharina Behr Josef Bischofberger Stephan Müller Tilo Kunath Klaus Christensen Anna Lisa Gündner Martin Graf Ravi Jagasia Verdon Taylor
author_facet	Stefania Fedele Ginetta Collo Katharina Behr Josef Bischofberger Stephan Müller Tilo Kunath Klaus Christensen Anna Lisa Gündner Martin Graf Ravi Jagasia Verdon Taylor
author_sort	Stefania Fedele
title	Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
title_short	Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
title_full	Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
title_fullStr	Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
title_full_unstemmed	Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
title_sort	expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5ed1c6e948cd4fae965b4783e0f2222b
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Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential

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