Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression
The common marmoset (<i>Callithrix jacchus</i>) 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 neurodegenerati...
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MDPI AG
2020-12-01
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| author | Akisa Nemoto Reona Kobayashi Sho Yoshimatsu Yuta Sato Takahiro Kondo Andrew S. Yoo Seiji Shiozawa Hideyuki Okano |
| author_facet | Akisa Nemoto Reona Kobayashi Sho Yoshimatsu Yuta Sato Takahiro Kondo Andrew S. Yoo Seiji Shiozawa Hideyuki Okano |
| author_sort | Akisa Nemoto |
| collection | DOAJ |
| description | The common marmoset (<i>Callithrix jacchus</i>) 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. |
| first_indexed | 2024-03-10T13:51:42Z |
| format | Article |
| id | doaj.art-b0c46f0478cb4ba394d31f1b318cf0f4 |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T13:51:42Z |
| publishDate | 2020-12-01 |
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| record_format | Article |
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| spelling | doaj.art-b0c46f0478cb4ba394d31f1b318cf0f42023-11-21T02:04:25ZengMDPI AGCells2073-44092020-12-01101610.3390/cells10010006Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 OverexpressionAkisa Nemoto0Reona Kobayashi1Sho Yoshimatsu2Yuta Sato3Takahiro Kondo4Andrew S. Yoo5Seiji Shiozawa6Hideyuki Okano7Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, JapanLaboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Wako City, Saitama 351-0198, JapanDepartment of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, JapanThe common marmoset (<i>Callithrix jacchus</i>) 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.https://www.mdpi.com/2073-4409/10/1/6direct reprogramminginduced neuron (iN)common marmosetmicroRNA-9/9*microRNA-124ASCL1 |
| spellingShingle | Akisa Nemoto Reona Kobayashi Sho Yoshimatsu Yuta Sato Takahiro Kondo Andrew S. Yoo Seiji Shiozawa Hideyuki Okano Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression Cells direct reprogramming induced neuron (iN) common marmoset microRNA-9/9* microRNA-124 ASCL1 |
| 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 | direct reprogramming induced neuron (iN) common marmoset microRNA-9/9* microRNA-124 ASCL1 |
| url | https://www.mdpi.com/2073-4409/10/1/6 |
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