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Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression

The common marmoset (Callithrix jacchus) has attracted considerable attention, especially in the biomedical science and neuroscience research fields, because of its potential to recapitulate the complex and multidimensional phenotypes of human diseases, and several neurodegenerative transgenic model...

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Autores principales: Nemoto, Akisa, Kobayashi, Reona, Yoshimatsu, Sho, Sato, Yuta, Kondo, Takahiro, Yoo, Andrew S., Shiozawa, Seiji, Okano, Hideyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822173/
https://www.ncbi.nlm.nih.gov/pubmed/33375083
http://dx.doi.org/10.3390/cells10010006
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author Nemoto, Akisa
Kobayashi, Reona
Yoshimatsu, Sho
Sato, Yuta
Kondo, Takahiro
Yoo, Andrew S.
Shiozawa, Seiji
Okano, Hideyuki
author_facet Nemoto, Akisa
Kobayashi, Reona
Yoshimatsu, Sho
Sato, Yuta
Kondo, Takahiro
Yoo, Andrew S.
Shiozawa, Seiji
Okano, Hideyuki
author_sort Nemoto, Akisa
collection PubMed
description The common marmoset (Callithrix jacchus) has attracted considerable attention, especially in the biomedical science and neuroscience research fields, because of its potential to recapitulate the complex and multidimensional phenotypes of human diseases, and several neurodegenerative transgenic models have been reported. However, there remain several issues as (i) it takes years to generate late-onset disease models, and (ii) the onset age and severity of phenotypes can vary among individuals due to differences in genetic background. In the present study, we established an efficient and rapid direct neuronal induction method (induced neurons; iNs) from embryonic and adult marmoset fibroblasts to investigate cellular-level phenotypes in the marmoset brain in vitro. We overexpressed reprogramming effectors, i.e., microRNA-9/9*, microRNA-124, and Achaete-Scute family bHLH transcription factor 1, in fibroblasts with a small molecule cocktail that facilitates neuronal induction. The resultant iNs from embryonic and adult marmoset fibroblasts showed neuronal characteristics within two weeks, including neuron-specific gene expression and spontaneous neuronal activity. As directly reprogrammed neurons have been shown to model neurodegenerative disorders, the neuronal reprogramming of marmoset fibroblasts may offer new tools for investigating neurological phenotypes associated with disease progression in non-human primate neurological disease models.
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spelling pubmed-78221732021-01-23 Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression Nemoto, Akisa Kobayashi, Reona Yoshimatsu, Sho Sato, Yuta Kondo, Takahiro Yoo, Andrew S. Shiozawa, Seiji Okano, Hideyuki Cells Article The common marmoset (Callithrix jacchus) has attracted considerable attention, especially in the biomedical science and neuroscience research fields, because of its potential to recapitulate the complex and multidimensional phenotypes of human diseases, and several neurodegenerative transgenic models have been reported. However, there remain several issues as (i) it takes years to generate late-onset disease models, and (ii) the onset age and severity of phenotypes can vary among individuals due to differences in genetic background. In the present study, we established an efficient and rapid direct neuronal induction method (induced neurons; iNs) from embryonic and adult marmoset fibroblasts to investigate cellular-level phenotypes in the marmoset brain in vitro. We overexpressed reprogramming effectors, i.e., microRNA-9/9*, microRNA-124, and Achaete-Scute family bHLH transcription factor 1, in fibroblasts with a small molecule cocktail that facilitates neuronal induction. The resultant iNs from embryonic and adult marmoset fibroblasts showed neuronal characteristics within two weeks, including neuron-specific gene expression and spontaneous neuronal activity. As directly reprogrammed neurons have been shown to model neurodegenerative disorders, the neuronal reprogramming of marmoset fibroblasts may offer new tools for investigating neurological phenotypes associated with disease progression in non-human primate neurological disease models. MDPI 2020-12-22 /pmc/articles/PMC7822173/ /pubmed/33375083 http://dx.doi.org/10.3390/cells10010006 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nemoto, Akisa
Kobayashi, Reona
Yoshimatsu, Sho
Sato, Yuta
Kondo, Takahiro
Yoo, Andrew S.
Shiozawa, Seiji
Okano, Hideyuki
Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
title Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
title_full Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
title_fullStr Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
title_full_unstemmed Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
title_short Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
title_sort direct neuronal reprogramming of common marmoset fibroblasts by ascl1, microrna-9/9*, and microrna-124 overexpression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822173/
https://www.ncbi.nlm.nih.gov/pubmed/33375083
http://dx.doi.org/10.3390/cells10010006
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