Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons

Abstract Directed differentiation of human pluripotent stem cells (hPSCs) has enabled the generation of specific neuronal subtypes that approximate the intended primary mammalian cells on both the RNA and protein levels. These cells offer unique opportunities, including insights into mechanistic und...

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Autores principales:	Daniel Moakley, Joan Koh, Joao D. Pereira, Daniel M. DuBreuil, Anna-Claire Devlin, Eugene Berezovski, Kevin Zhu, Brian J. Wainger
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/61fc65bb89e1477982eb7445731e61fc
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spelling	oai:doaj.org-article:61fc65bb89e1477982eb7445731e61fc2021-12-02T16:07:53ZPharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons10.1038/s41598-019-47203-72045-2322https://doaj.org/article/61fc65bb89e1477982eb7445731e61fc2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47203-7https://doaj.org/toc/2045-2322Abstract Directed differentiation of human pluripotent stem cells (hPSCs) has enabled the generation of specific neuronal subtypes that approximate the intended primary mammalian cells on both the RNA and protein levels. These cells offer unique opportunities, including insights into mechanistic understanding of the early driving events in neurodegenerative disease, replacement of degenerating cell populations, and compound identification and evaluation in the context of precision medicine. However, whether the derived neurons indeed recapitulate the physiological features of the desired bona fide neuronal subgroups remains an unanswered question and one important for validating stem cell models as accurate functional representations of the primary cell types. Here, we purified both hPSC-derived and primary mouse spinal motor neurons in parallel and used extracellular multi-electrode array (MEA) recording to compare the pharmacological sensitivity of neuronal excitability and network function. We observed similar effects for most receptor and channel agonists and antagonists, supporting the consistency between human PSC-derived and mouse primary spinal motor neuron models from a physiological perspective.Daniel MoakleyJoan KohJoao D. PereiraDaniel M. DuBreuilAnna-Claire DevlinEugene BerezovskiKevin ZhuBrian J. WaingerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Moakley Joan Koh Joao D. Pereira Daniel M. DuBreuil Anna-Claire Devlin Eugene Berezovski Kevin Zhu Brian J. Wainger Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons
description	Abstract Directed differentiation of human pluripotent stem cells (hPSCs) has enabled the generation of specific neuronal subtypes that approximate the intended primary mammalian cells on both the RNA and protein levels. These cells offer unique opportunities, including insights into mechanistic understanding of the early driving events in neurodegenerative disease, replacement of degenerating cell populations, and compound identification and evaluation in the context of precision medicine. However, whether the derived neurons indeed recapitulate the physiological features of the desired bona fide neuronal subgroups remains an unanswered question and one important for validating stem cell models as accurate functional representations of the primary cell types. Here, we purified both hPSC-derived and primary mouse spinal motor neurons in parallel and used extracellular multi-electrode array (MEA) recording to compare the pharmacological sensitivity of neuronal excitability and network function. We observed similar effects for most receptor and channel agonists and antagonists, supporting the consistency between human PSC-derived and mouse primary spinal motor neuron models from a physiological perspective.
format	article
author	Daniel Moakley Joan Koh Joao D. Pereira Daniel M. DuBreuil Anna-Claire Devlin Eugene Berezovski Kevin Zhu Brian J. Wainger
author_facet	Daniel Moakley Joan Koh Joao D. Pereira Daniel M. DuBreuil Anna-Claire Devlin Eugene Berezovski Kevin Zhu Brian J. Wainger
author_sort	Daniel Moakley
title	Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons
title_short	Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons
title_full	Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons
title_fullStr	Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons
title_full_unstemmed	Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons
title_sort	pharmacological profiling of purified human stem cell-derived and primary mouse motor neurons
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/61fc65bb89e1477982eb7445731e61fc
work_keys_str_mv	AT danielmoakley pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT joankoh pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT joaodpereira pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT danielmdubreuil pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT annaclairedevlin pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT eugeneberezovski pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT kevinzhu pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons AT brianjwainger pharmacologicalprofilingofpurifiedhumanstemcellderivedandprimarymousemotorneurons
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Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons

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