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SHANK2 LOSS IMPAIRS NEURITE OUTGROWTH AND INSULIN SIGNALLING PATHWAYS IN HUMAN IPSC-DERIVED NEURAL STEM CELLS
Chang Liuand 6 co-authors
Institute of Human Genetics, University Hospital Heidelberg
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS06-09PM-309
Presentation
Date TBA
Board: PS06-09PM-309
Event Information
Poster Board
PS06-09PM-309
Poster
View posterAbstract
SHANK2 is a postsynaptic scaffold protein with an important role in synapse formation, function and plasticity. Genetic variants in SHANK2 have been strongly implicated in neurodevelopmental disorders including autism spectrum disorder and intellectual disability. While SHANK2 function has been extensively studied in neurons, its contribution to early human neural development remains poorly understood. To investigate the role of SHANK2 during early neurodevelopment, we generated heterozygous and homozygous SHANK2 knockout human induced pluripotent stem cells using CRISPR–Cas9 genome editing, and differentiated them into neural stem cells (NSCs). Both heterozygous and homozygous SHANK2-deficient NSCs showed significant impairments in neurite outgrowth and cell adhesion, as quantified by IncuCyte-based live-cell imaging and cell spreading assays. qPCR and western blot analyses revealed disrupted insulin receptor signaling, with significantly increased insulin receptor transcript levels and reduced basal AKT and MAPK phosphorylation.
Together, these findings identify SHANK2 as a critical regulator of early human NSC development and suggest that SHANK2-associated neurodevelopmental disorders may originate at progenitor stages preceding synapse formation. Ongoing and future work will integrate transcriptomic profiling and direct comparisons with patient-derived NSCs to validate disease relevance and further delineate SHANK2-dependent mechanisms governing early human neural development.
Together, these findings identify SHANK2 as a critical regulator of early human NSC development and suggest that SHANK2-associated neurodevelopmental disorders may originate at progenitor stages preceding synapse formation. Ongoing and future work will integrate transcriptomic profiling and direct comparisons with patient-derived NSCs to validate disease relevance and further delineate SHANK2-dependent mechanisms governing early human neural development.
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