Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Simple Differentiation Protocol for Generation of Induced Pluripotent Stem Cell-derived Basal Forebrain Cholinergic Neurons for Alzheimer’s Disease and Frontotemporal Dementia Disease Modeling

Version 1 : Received: 3 August 2020 / Approved: 4 August 2020 / Online: 4 August 2020 (11:17:44 CEST)

A peer-reviewed article of this Preprint also exists.

Muñoz, S.S.; Engel, M.; Balez, R.; Do-Ha, D.; Cabral-da-Silva, M.C.; Hernández, D.; Berg, T.; Fifita, J.A.; Grima, N.; Yang, S.; Blair, I.P.; Nicholson, G.; Cook, A.L.; Hewitt, A.W.; Pébay, A.; Ooi, L. A Simple Differentiation Protocol for Generation of Induced Pluripotent Stem Cell-Derived Basal Forebrain-Like Cholinergic Neurons for Alzheimer’s Disease and Frontotemporal Dementia Disease Modeling. Cells 2020, 9, 2018. Muñoz, S.S.; Engel, M.; Balez, R.; Do-Ha, D.; Cabral-da-Silva, M.C.; Hernández, D.; Berg, T.; Fifita, J.A.; Grima, N.; Yang, S.; Blair, I.P.; Nicholson, G.; Cook, A.L.; Hewitt, A.W.; Pébay, A.; Ooi, L. A Simple Differentiation Protocol for Generation of Induced Pluripotent Stem Cell-Derived Basal Forebrain-Like Cholinergic Neurons for Alzheimer’s Disease and Frontotemporal Dementia Disease Modeling. Cells 2020, 9, 2018.

Journal reference: Cells 2020, 9, 2018
DOI: 10.3390/cells9092018

Abstract

The study of neurodegenerative diseases using pluripotent stem cells requires new methods to assess neurodevelopment and neurodegeneration of specific neuronal subtypes. The cholinergic system, characterized by its use of the neurotransmitter acetylcholine, is one of the first to degenerate in Alzheimer’s disease and is also affected in frontotemporal dementia. We developed a differentiation protocol to generate basal forebrain cholinergic neurons (BFCNs) from induced pluripotent stem cells (iPSCs) aided by the use of small molecule inhibitors and growth factors. Ten iPSC lines were successfully differentiated into BFCNs using this protocol. The neuronal cultures were characterised through RNA and protein expression, and functional analysis of neurons was confirmed by whole-cell patch clamp. We have developed a reliable protocol using only small molecule inhibitors and growth factors, while avoiding transfection or cell sorting methods, to achieve a BFCN culture that expresses the characteristic markers of cholinergic neurons.

Subject Areas

induced pluripotent stem cells; disease modelling; neuronal differentiation; cholinergic neurons; Alzheimer’s disease; frontotemporal dementia

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.