Stanford Tissue Mapping Center

摘要：总体 小肠和结肠是维持人体内环境稳定的关键器官。 在摄取食物时调节营养吸收。尽管这两个器官的长度都很长， 每个细胞的不同部分在功能和细胞异质性方面都有已知的差异。另外， 肠内任何一处的横切面显示了参与吸收的成分的复杂分层。 以及分泌物、肠道内容物的运动、循环和免疫。在本意见书中，我们建议 建立斯坦福组织测绘中心(TMC)以绘制小组织的复杂性 肠和结肠组织切片中细胞对细胞的分辨率，无论是沿其长度还是横向 多个个体。为了实现这一目标，我们将收集脑死亡器官捐赠者的组织 明确同意在HuBMAP联盟之间分发和开放获取基因组数据共享 (GDS)。然后将采用两套技术。组织样本将接受单细胞培养 (Sc)atac-seq和scRNA-seq.然后，这些基因组图谱将被空间映射回组织学 使用高度多元化的抗体标记的目标表位系统的部分，我们称之为 索引联合检测(CODEX)。将进行综合分析以识别蛋白质 对于确定组织内每个细胞群体的身份很重要。 ​

ABSTRACT: Overall The small bowel and colon are organs critical for maintaining homeostasis of the human body by mediating nutritional absorption upon the ingestion of food. Though both organs are extensive in length, there are known differences in function and cellular heterogeneity within different portions of each. Also, a cross section anywhere in the bowel reveals a complex layering of components involved in absorption and secretion, motility of gut contents, circulation, and immunity. In this submission, we propose the establishment of the Stanford Tissue Mapping Center (TMC) to map the complexity of the the small bowel and colon with cell-to-cell resolution in histologic sections, both along their lengths and across multiple individuals. To accomplish this goal, we will collect tissues from brain-dead organ donors with explicit consent for distribution among the HuBMAP consortium and open access genome data sharing (GDS). Two sets of technologies will then be employed. Tissue samples will be subjected to single cell (sc) ATAC-seq and scRNA-seq. These ‘omic profiles will then be spatially mapped back to histologic sections using a highly multiplexed system of antibody-tagged target epitopes, which we call CO-Detection by indEXing (CODEX). An integrative analysis will be performed to identify proteins important to establishing the identity of each cell population within the tissue. ​