Poster #078, UC Davis Health System
Validation of iPSCs as Human Cell Model for Future CHAT-Associated Studies
Mentor: Junjing Jia, PhD
The CHAT gene encodes choline acetyltransferase, the enzyme required for acetylcholine synthesis and normal communication in the central and peripheral nervous systems. Pathogenic CHAT variants can cause presynaptic congenital myasthenic syndrome type 6 (CMS6), characterized by fatigable muscle weakness and respiratory complications. This study aimed to establish and characterize a patient-specific induced pluripotent stem cell (iPSC) model of CHAT-related disease. Dermal fibroblasts from patient CHAT 6, who carries pathogenic CHAT variants, were reprogrammed into iPSCs. Colonies with typical stem cell morphology were selected, expanded, and evaluated by morphological assessment and immunofluorescence staining for pluripotency-associated protein markers. The developmental potential of the iPSCs was further assessed through differentiation into ectoderm, mesoderm, and endoderm, followed by lineage-specific marker analysis. These experiments were designed to confirm successful reprogramming and pluripotency. The validated patient-derived iPSC line provides a renewable human cell model for future studies of CHAT-associated disease mechanisms, comparison with healthy control cells, differentiation into disease-relevant cell types, and evaluation of potential therapeutic strategies.