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

The common marmoset ( ) 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 repor...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2020-12, Vol.10 (1), p.6
Main Authors: Nemoto, Akisa, Kobayashi, Reona, Yoshimatsu, Sho, Sato, Yuta, Kondo, Takahiro, Yoo, Andrew S, Shiozawa, Seiji, Okano, Hideyuki
Format: Article
Language:English
Subjects:
Animals
ASCL1
Basic Helix-Loop-Helix Transcription Factors - metabolism
Callithrix
Cells, Cultured
Cellular Reprogramming
common marmoset
direct reprogramming
Disease Models, Animal
Fibroblasts
induced neuron (iN)
microRNA-124
microRNA-9/9
MicroRNAs
Nervous System Diseases - metabolism
Neurons - metabolism
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Summary:The common marmoset ( ) 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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10010006