Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes

Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes

The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential...

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Main Authors: Imaizumi, Kent, Sone, Takefumi, Ibata, Keiji, Fujimori, Koki, Yuzaki, Michisuke, Akamatsu, Wado, Okano, Hideyuki
Format: Online
Language:English
Published: Elsevier 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682123/
id pubmed-4682123
recordtype oai_dc
spelling pubmed-46821232016-01-12 Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes Imaizumi, Kent Sone, Takefumi Ibata, Keiji Fujimori, Koki Yuzaki, Michisuke Akamatsu, Wado Okano, Hideyuki Article The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs. Elsevier 2015-11-05 /pmc/articles/PMC4682123/ /pubmed/26549851 http://dx.doi.org/10.1016/j.stemcr.2015.10.005 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Imaizumi, Kent
Sone, Takefumi
Ibata, Keiji
Fujimori, Koki
Yuzaki, Michisuke
Akamatsu, Wado
Okano, Hideyuki
spellingShingle Imaizumi, Kent
Sone, Takefumi
Ibata, Keiji
Fujimori, Koki
Yuzaki, Michisuke
Akamatsu, Wado
Okano, Hideyuki
Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
author_facet Imaizumi, Kent
Sone, Takefumi
Ibata, Keiji
Fujimori, Koki
Yuzaki, Michisuke
Akamatsu, Wado
Okano, Hideyuki
author_sort Imaizumi, Kent
title Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
title_short Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
title_full Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
title_fullStr Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
title_full_unstemmed Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
title_sort controlling the regional identity of hpsc-derived neurons to uncover neuronal subtype specificity of neurological disease phenotypes
description The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.
publisher Elsevier
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682123/
_version_ 1613513702137397248

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