Defining the intestinal stem cell niche during organoid development into a functional human intestine

摘要 这一建议利用了我们最近开发的体外培养人类多能干细胞的方法。 衍生的肠道和结肠器官(HIO/HCO)，与我们独特的器官移植相结合 识别支持小细胞和大细胞的特定间充质和内胚层壁龛细胞类型的模型 肠子。在肠道干细胞联盟(ISCC)内完成的这项工作的临床意义在于它 将帮助我们的团队确定最佳的ISC利基组件，从而支持 功能性人类区域化肠道移植及再生损伤所需的治疗 肠子。我们的初步数据表明，记者工具和重组的成功开发 用尖端分子方法定位特定间充质和内胚层种群的方法 确定支持人类ISC的特定信号通路和活体人类肠道模型进行研究 全身化疗后的再生。

Abstract This proposal capitalizes on our recently developed in vitro methods to culture human pluripotent stem cell derived intestinal and colonic organoids (HIO/HCO), combined with our unique organoid transplantation models to identify specific mesenchymal and endodermal niche cell types that support the small and large intestine. The clinical relevance of this work done within the Intestinal Stem Cell Consortium (ISCC) is that it will contribute to our groups effort to identify optimal ISC niche components that will enable both transplantation of functional human regionalized intestine and inform therapies required to regenerate damage intestine. Our preliminary data demonstrates the successful development of reporter tools and recombination assays to localize specific mesenchymal and endodermal populations with cutting edge molecular approaches to identify specific signal pathways supporting the human ISC and in vivo human intestinal models to study regeneration following systemic administration of chemotherapy.