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Oral Sessions
Day 3, June 24（Tue.） 14:25-14:40
Room A (Maesato West)
- 3A-O2-1425
Quantitative proteomic analysis of SCN1A gene knockout in cerebral organoids during differentiation for underlying Dravet syndrome
(1KRISS, 2KRICT, 3GIST)
Young Eun Kim1,3, Byunmseok Koh2, Sung Bum Park2, Sung-Hee Cho2, Tae-Young Kim3, Myung Ae Bae2, Ki Young Kim2, oDukjin Kang1
Developing three-dimensional (3D) cell culture platforms in both drug screening and toxicology has gradually gained of interest. In this regard, analytical strategie(s) and alternative pivotal biomarker(s) in assessing the maturity and functionality of 3D-cultured organoids and their similarities to actual human organs is inevitably required. In this presentation, we introduce a quantitative proteomic analysis of SCN1A gene knockout in cerebral organoids representing Dravet syndrome model and their ordinary counterparts (days 0 and 120) using online 2D-nanoLC-ESI-MS/MS with isobaric labeling to investigate the impact of sodium channel protein type 1 subunit alpha (SCN1A). As a result, a total of 5870 proteins, each with at least two peptides and three iTRAQ values, were commonly quantified in both SCN1A-KO and controls. From this quantitative profiling of cerebral organoid proteome, we found that the expression levels of the SCN1A KO organoid proteome shows perturbations in cholesterol metabolism and sodium ion transportation, thereby potentially affecting synaptic transmission. Taken together, these findings deepen our understanding of the molecular mechanisms underlying SCN1A-associated disorders in Dravet syndrome and offer strategies for developing psychiatric organoid models for drug screening.