Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells

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. We established a novel protocol to differentiate visceral sensory ganglion organoid (VSGOs) and induced-visceral sensory neurons (i-VSNs) from induced pluripotent stem cells (iPSCs). VSGOs and i-VSNs among two isogenic iPSC lines (E3, E4), progenitors of VSGOs (Otic-epibranchial progenitor domain(OEPD), Epibranchial placode(EpP) were analyzed using single cell and single nucleus RNA sequencing. Additional information can be found in the supplementary files attached to the article.