The single and same cell 3D atlas of epigenome and transcriptome of the lower urinary tract

回应RFA-DK-20-013“泌尿生殖系统发育分子解剖学项目（GUDMAP）- Atlas 项目”，该提案旨在“生成数据以可视化发育中的泌尿道， 和解剖结构域以及细胞类型”。胚胎的后肠或泄殖腔由一个中空的 两个独立的实体-泌尿道和肛门直肠道。泌尿道进一步分化为 嘴侧的膀胱和尾侧的生殖器尿道。在组织特异性基因表达模式的指导下， 显示了几种选定的转录因子和信号分子对泌尿道发育至关重要 并且是造成人类一些最复杂的先天缺陷的原因。然而，这些低吞吐量和 孤立的案例研究提供的信息有限，很难将这些发现整合起来， 基因-细胞关系在发育和疾病中的作用。资源包括所有基因的空间注释 细胞是必需的。利用包括单细胞多组学和空间转录组学在内的创新技术， 应用程序旨在1）从小鼠下尿路的所有细胞中创建一系列数字库，其中每个 细胞基于其自身的转录组学和表观基因组学谱进行注释; 2）产生超高密度组织- 下尿路的特异性空间转录组图谱;以及3）在近单个水平显示空间转录组 细胞分辨率到3D数字化小鼠和人类胚胎上。这些资源将用于研究 社区建立一个全面的了解尿路发育，包括但不限于 泄殖腔分隔和泌尿道分化。

In response to RFA-DK-20-013 “GenitoUrinary Development Molecular Anatomy Project (GUDMAP) - Atlas Projects”, this proposal aims “to generate data to visualize the developing urinary tract, to identify new functional and anatomical domains, and cell types”. The embryonic hindgut or cloaca progresses from a single hollow organ to two separate entities – the urinary tract and anorectal tract. The urinary tract further differentiates into the bladder rostrally and the genital urethra caudally. Guided by tissue-specific gene expression patterns, we show that several selected transcription factors and signaling molecules are critical for urinary tract development and, are responsible for some of the most complex human birth defects. However, these low-throughput and isolated case studies offer limited information; and it is difficult integrate these findings to discern gene-gene and gene-cell relationships in development and in disease. Resources including spatial annotation of all genes in all cells are needed. Using innovative technologies including single cell Multi-omics and Spatial Transcriptome, this application aims to 1) create a series of digital libraries from all cells of mouse lower urinary tract, in which every cell is annotated based on its' own transcriptomic and epigenomic profiles; 2) generate ultrahigh-density tissue- specific spatial transcriptomic map of the lower urinary tract; and 3) display spatial transcriptome at near single cell resolution onto the 3D digitalized mouse and human embryos. These resources will serve the research community to establish a comprehensive understanding of urinary tract development, including but not limited to cloaca septation and urinary tract differentiation.