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Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA

Lookup NU author(s): Dr Polina YarovaORCiD, Dr Seva TelezhkinORCiD

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley-Blackwell Publishing Ltd., 2016.

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Abstract

Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronize the neurogenesis of pluripotent stem cell-derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines. Such enhanced rate and extent of synchronized maturation of pluripotent stem cell-derived neural progenitor cells generates neurons which are characterized by a relatively hyperpolarized resting membrane potential, higher spontaneous and induced action potential activity, enhanced synaptic activity, more complete development of a mature inhibitory GABA_A receptor phenotype and faster production of electrical network activity when compared to standard differentiation media. This entire process - from pre-patterned neural progenitor to active neuron - takes 3 weeks or less, making it an ideal platform for drug discovery and disease modelling in the fields of human neurodegenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia.

Publication metadata

Author(s): Kemp PJ, Rushton DJ, Yarova PL, Schnell C, Geater C, Hancock JM, Wieland A, Hughes A, Badder L, Cope E, Riccardi D, Randall AD, Brown JT, Allen ND, Telezhkin V

Publication type: Article

Publication status: Published

Journal: The Journal of Physiology

Year: 2016

Volume: 594

Issue: 22

Pages: 6583-6594

Print publication date: 15/11/2016

Online publication date: 12/09/2016

Acceptance date: 23/08/2016

Date deposited: 10/03/2017

ISSN (print): 0022-3751

ISSN (electronic): 1469-7793

Publisher: Wiley-Blackwell Publishing Ltd.

URL: https://doi.org/10.1113/JP270655

DOI: 10.1113/JP270655

PubMed id: 27616476

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