Molecular Therapy: Nucleic Acids (Mar 2025)
Multi-omic insights into molecular mechanism and therapeutic targets in spinocerebellar ataxia type 7
- Soo Hyun Ahn,
- Yoonhyuk Jang,
- Bum-Sup Jang,
- Jangsup Moon,
- Woo-Jin Lee,
- Dong-Kyu Park,
- Jung-Suk Yu,
- Hyoshin Son,
- Hyeyoon Kim,
- Dohyun Han,
- Heeyoung Seok,
- Yongmoo Kim,
- Seo-Yi Shin,
- Soon-Tae Lee,
- Kyung-Il Park,
- Keun-Hwa Jung,
- Daejong Jeon,
- Sang Kun Lee,
- Kon Chu
Affiliations
- Soo Hyun Ahn
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea
- Yoonhyuk Jang
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea; The National Strategic Technology Research Institute, Seoul 03080, Republic of Korea
- Bum-Sup Jang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Jangsup Moon
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea; Department of Genomic Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Woo-Jin Lee
- Department of Neurology, Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea
- Dong-Kyu Park
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea; Advanced Neural Technologies, Seoul 03087, Republic of Korea
- Jung-Suk Yu
- Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea; Advanced Neural Technologies, Seoul 03087, Republic of Korea
- Hyoshin Son
- Department of Neurology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Republic of Korea
- Hyeyoon Kim
- Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea; Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea
- Dohyun Han
- Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea; Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea
- Heeyoung Seok
- Department of Transdisciplinary Research and Collaboration, Genomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea
- Yongmoo Kim
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea
- Seo-Yi Shin
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea
- Soon-Tae Lee
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea
- Kyung-Il Park
- Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Republic of Korea
- Keun-Hwa Jung
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea
- Daejong Jeon
- Advanced Neural Technologies, Seoul 03087, Republic of Korea
- Sang Kun Lee
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea
- Kon Chu
- Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy Center, Center for Medical Innovation, Biomedical Research Institute, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea; Corresponding author: Kon Chu, MD, PhD, Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
- Journal volume & issue
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Vol. 36,
no. 1
p. 102414
Abstract
Recent advances in molecular science have significantly enlightened our mechanistic understanding of spinocerebellar ataxia type 7. To further close remaining gaps, we performed a multi-omics analysis using SCA7266Q/5Q mice. Entire brain tissue samples were collected from 12-week-old mice, and RNA sequencing, methylation analysis, and proteomic analysis were performed. Results were integrated to identify genes with identical trends in expression across all three analyses. Data from RNA sequencing and methylation analysis revealed 58 significantly hypomethylated-upregulated genes and 62 hypermethylated-downregulated genes, mostly enriched in GO terms of regulation of axonogenesis, channel activity, and monoamine signaling. In the proteomic analysis, 211 upregulated and 281 downregulated DEPs associated mostly with immune response and cellular mobility were identified. Two genes, Fam107b and Tph2, showed differential expressions in both transcriptomic and proteomic analyses. Findings were validated in RT-qPCR as well as open data source analysis. Our study is the first to perform multi-omics analysis in SCA7 mice and will serve as an important reference for future studies.
