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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

Muñoz, SS, Engel, M, Balez, R, Do-Ha, D, Cabral-da-Silva, MC, Hernández, D, Berg, T, Fifita, JA, Grima, N, Yang, S, Blair, IP, Nicholson, G, Cook, AL, Hewitt, AW, Pébay, A and Ooi, L 2020, 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, vol. 9, no. 9, pp. 1-17, doi: 10.3390/cells9092018.

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Title 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
Author(s) Muñoz, SS
Engel, M
Balez, R
Do-Ha, D
Cabral-da-Silva, MC
Hernández, D
Berg, T
Fifita, JA
Grima, N
Yang, S
Blair, IP
Nicholson, G
Cook, AL
Hewitt, AW
Pébay, A
Ooi, L
Journal name Cells
Volume number 9
Issue number 9
Article ID 2018
Start page 1
End page 17
Total pages 17
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2020
ISSN 2073-4409
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Cell Biology
induced pluripotent stem cells
disease modelling
neuronal differentiation
cholinergic neurons
Alzheimer's disease
frontotemporal dementia
APOLIPOPROTEIN-E
TYPE-4 ALLELE
5-FLUORO-2'-DEOXYURIDINE
PROLIFERATION
EXPRESSION
BIOLOGY
EMX1
Alzheimer’s disease
Summary 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.
Language eng
DOI 10.3390/cells9092018
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30164046

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Citation counts: TR Web of Science Citation Count  Cited 7 times in TR Web of Science
Scopus Citation Count Cited 9 times in Scopus Google Scholar Search Google Scholar
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.