Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells[chip_scRNAseq]

The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem (iPS) cells may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders. We established a protocol to differentiate human iPS-cell-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 iPS cells, which demonstrated a strong correlation with clinical data. Five chips were collected to create each library. For each chamber of the axis-on-a-chip, single-nucleus sequencing of VSGO and single-cell RNA sequencing of iPSC-derived colon organoids were performed. Additional information can be found in the supplementary files attached to the article.