The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem cells (iPSCs) may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders.
We established a protocol to differentiate human iPSC-derived visceral sensory ganglion organoids (VSGOs). VSGOs exhibit canonical VSN markers, and single-cell RNA sequencing revealed heterogenous molecular signatures and developmental trajectories of VSGOs aligned with native VSN.
We integrated VSGOs with human colon organoids on a microfluidic device and applied this axis-on-a-chip model to Alzheimer’s disease. Our results suggest that VSN could be a potential mediator for propagating gut-derived amyloid and tau to the brain in an APOE4 and LRP1 dependent manner.
Furthermore, our approach was extended to include patient-derived iPSCs, which demonstrated a strong correlation with clinical data.

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