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CONSTRUCTION OF HUMAN CHOLINERGIC PROJECTIONS IN NBM-CORTICAL ASSEMBLOIDS REVEAL PROJECTIVE DEFECTS IN DOWN SYNDROME
Da Wangand 2 co-authors
Nanjing Medical University
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS04-08PM-171
Presentation
Date TBA
Board: PS04-08PM-171
Event Information
Poster Board
PS04-08PM-171
Poster
View posterAbstract
Down syndrome is a disorder caused by an additional full or partial copy of chromosome 21. This chromosomal variation leads to notable developmental and intellectual challenges. Medical imaging indicates that those with Down syndrome often experience a reduction in volume across several areas of the nucleus basalis of Meynert (nbM). These structural changes are believed to contribute to the cognitive difficulties observed in Down syndrome. However, the precise molecular processes that underlie these developmental issues have yet to be fully understood. Here we developed a approach for differentiating human pluripotent stem cells into human nucleus basalis of Meynert organoids (hnbMOs) with subregional identity by treating sonic hedgehog (SHH) to ventralize the neural tube. Then we fused hnbMOs with human cortex organoids (hCOs) to form assembloids. We validate the structural and functional connectivity of nbM cholinergic neurons to the cortex in assembloids. In addition, we identified neural morphological and projective defects in cholinergic neurons in Down syndrome patient iPSC-derived assembloids. Our work simulates the abnormalities in the cholinergic circuit between the nbM and cortex in Down syndrome through the application of organoids and assembloids.
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