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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

Citation

Munoz, SS and Engel, M and Balez, R and Do-Ha, D and Cabral-da-Silva, MC and Hernandez, D and Berg, T and Fifita, JA and Grima, N and Yang, S and Blair, IP and Nicholson, G and Cook, AL and Hewitt, AW and Pebay, A and 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, 9, (9) Article E2018. ISSN 2073-4409 (2020) [Refereed Article]


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Copyright 2020 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: 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-like 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.

Item Details

Item Type:Refereed Article
Keywords:stem cell, disease model, Alzheimerís disease, cholinergic neurons, disease modelling, frontotemporal dementia, induced pluripotent stem cells, neuronal differentiation
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Cook, AL (Associate Professor Tony Cook)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:140751
Year Published:2020
Web of Science® Times Cited:4
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2020-09-03
Last Modified:2020-10-27
Downloads:2 View Download Statistics

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