Unraveling the Molecular Landscape of SCN1A Gene Knockout in Cerebral Organoids: A Multiomics Approach Utilizing Proteomics, Lipidomics, and Transcriptomics
This study investigates the impact of sodium channel protein type 1 subunit alpha (SCN1A) gene knockout (SCN1A KO) on brain development and function using cerebral organoids coupled with a multiomics approach. From comprehensive omics analyses, we found that SCN1A KO organoids exhibit decreased growth, dysregulated neurotransmitter levels, and altered lipidomic, proteomic, and transcriptomic profiles compared to controls under matrix-free differentiation conditions. Neurochemical analysis reveals reduced levels of key neurotransmitters, and lipidomic analysis highlights changes in ether phospholipids and sphingomyelin. Furthermore, quantitative profiling of the SCN1A KO organoid proteome shows perturbations in cholesterol metabolism and sodium ion transportation, potentially affecting synaptic transmission. These findings suggest dysregulation of cholesterol metabolism and sodium ion transport, with implications for synaptic transmission. Overall, these insights shed light on the molecular mechanisms underlying SCN1A-associated disorders, such as Dravet syndrome, and offer potential avenues for therapeutic intervention.
Authors
- Seong Soon Kim (ORCID: https://orcid.org/0000-0002-4762-8693)
- Byumseok Koh (ORCID: https://orcid.org/0000-0002-1106-1891)
- Sung Bum Park (ORCID: https://orcid.org/0000-0001-8066-0129)
- Sung‐Hee Cho (ORCID: https://orcid.org/0000-0002-9605-5086)
- Dong Hyuck Bae (ORCID: https://orcid.org/0000-0002-1511-0558)
- Myung Ae Bae (ORCID: https://orcid.org/0000-0002-2997-5018)
- Jangjae Lee (ORCID: https://orcid.org/0000-0002-0298-5638)
- Tae‐Young Kim (ORCID: https://orcid.org/0000-0002-8846-3338)
- Young Eun Kim (ORCID: https://orcid.org/0000-0002-7182-6569)
- Kyung Jin Lee (ORCID: https://orcid.org/0000-0002-6709-3235)
- Jeong Hyeon Jo
- Ki Young Kim (ORCID: https://orcid.org/0000-0001-7868-2345)
- Dukjin Kang
Institutions
- Chungnam National University (KR)
- Korea University (KR)
- Korea Research Institute of Standards and Science (KR)
- Gwangju Institute of Science and Technology (KR)
- CHA University (KR)
- Korea Research Institute of Chemical Technology (KR)
Publication Details
- Journal
- ACS Omega
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1021/acsomega.4c05039
- Citations
- 1
- Primary Topic
- Cellular transport and secretion
- Type
- article
- Field-Weighted Citation Impact
- 0.33
Funders
- Chungnam National University
- Gwangju Institute of Science and Technology
- Korea University
- Ministry of Trade, Industry and Energy
- Korea Research Institute of Chemical Technology
- Korea Research Institute of Standards and Science
- CHA University
- Ministry of Science and ICT, South Korea