韩国首尔大学Inhee Mook-Jung等研究人员合作，从诱导性多能干细胞分化出内脏感觉神经节类器官。该研究于2024年10月22日在线发表于国际一流学术期刊《自然—方法学》。

研究人员建立了一种分化人类诱导性多能干细胞（iPS细胞）细胞来源的内脏感觉神经节类器官（VSGO）的方案。VSGO展现了典型的内脏感觉神经元（VSN）标记物。单细胞RNA测序揭示了与原生VSN一致的异质分子特征和发育轨迹。

研究人员将VSGO与人类结肠类器官集成在微流控设备上，并将该轴芯片模型应用于阿尔茨海默病。

结果表明，VSN可能通过依赖APOE4和LRP1的方式促进肠源性淀粉样蛋白和tau向大脑传播。此外，该研究方法可扩展到包括患者来源的iPS细胞，显示出与临床数据的强相关性。

据了解，从iPS细胞生成VSN的能力可能有助于深入了解肠–神经–大脑轴在神经系统疾病中的作用。

附：英文原文

Title: Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells

Author: 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

Issue&Volume: 2024-10-22

Abstract: 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.

DOI: 10.1038/s41592-024-02455-8

Source: https://www.nature.com/articles/s41592-024-02455-8