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

定义类器官发育成功能性人类肠道过程中的肠道干细胞生态位

• 批准号: 10470135
• 负责人: MICHAEL A. HELMRATH
• 金额: $ 39.73万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470135
• 关键词: Affect; Alginates; Animals; Attenuated; Automobile Driving; Award; Biological Assay; Cell Differentiation process; Cells; Collaborations; Cues; Data; Development; Disease; Endoderm; Engraftment; Enteral; Epithelial; Exposure to; FOXL1 gene; Generations; Genetic; Genetic Recombination; Genetic Transcription; Goals; Growth; Human; In Vitro; Individual; Injury; Intestines; Label; Large Intestine; Mesenchymal; Mesenchyme; Methods; Michigan; Modeling; Molecular; Mus; Natural regeneration; Neurons; Organoids; Pathway interactions; Patients; Platelet-Derived Growth Factor alpha Receptor; Pluripotent Stem Cells; Population; Regenerative research; Reporter; Signal Pathway; Signal Transduction; Small Intestines; Testing; Three-Dimensional Imaging; Time; Tissue Transplantation; Tissues; Translations; Transplantation; Villus; Vision; Work; base; cell type; chemotherapy; clinically relevant; cytokine; deep sequencing; fetal; human pluripotent stem cell; in vivo; intestinal epithelium; member; multidisciplinary; new therapeutic target; novel; organoid transplantation; parent grant; preclinical study; programs; reconstitution; regenerative; single-cell RNA sequencing; stem cell niche; stem cell technology; stem cells; tool; transcriptome; transplant model

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.

摘要 该方案利用我们最近开发的体外培养人多能干细胞的方法 肠和结肠类器官（HIO/HCO），结合我们独特的类器官移植 模型，以确定特定的间充质和内胚层小生境细胞类型，支持小和大的 肠子在肠干细胞联盟（ISCC）内完成的这项工作的临床相关性在于， 我将帮助我们的小组努力确定最佳的ISC利基组件， 移植功能性人类区域化肠和再生损伤所需的信息疗法 肠子我们的初步数据证明了报告工具和重组的成功发展 用尖端分子方法定位特定间充质和内胚层群体的测定 确定支持人ISC和体内人肠道模型研究的特定信号通路 全身性化疗后的再生。