Nature methods · 2024
Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells.
СтатьяНазвание и аннотация: Перевод в очереди
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Ahn Kyusik, Park Hwee-Seon, Choi Sieun, Lee Hojeong, Choi Hyunjung, Hong Seok Beom, Han Jihui, Han Jong Won, Ahn Jinchul, Song Jaehoon, Park Kyunghyuk, Cha Bukyung, Kim Minseop, Liu Hui-Wen, Song Hyeonggyu, Kim Sang Jeong, Chung Seok, Kim Jong-Il, Mook-Jung Inhee
Аннотация
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.