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计划(GUDMAP)-图集》 项目“，这项提案旨在”产生数据，以可视化的发展中的尿路，确定新的功能 和解剖领域，以及细胞类型“。胚胎的后肠或泄殖腔是从一个单一的空洞进化而来的。 器官转移到两个独立的实体--尿路和肛门直肠。尿路进一步分化为 膀胱头端和生殖器尿道尾。在组织特异性基因表达模式的指导下，我们 表明几个选定的转录因子和信号分子对尿路发育至关重要 并对一些最复杂的人类先天缺陷负有责任。然而，这些低吞吐量和 孤立的案例研究提供的信息有限；而且很难整合这些发现来识别基因-基因和 发育和疾病中的基因-细胞关系。包括所有基因的空间注释在内的资源 细胞是必需的。利用包括单细胞多组学和空间转录组在内的创新技术，这 应用程序的目标是1)利用小鼠下尿路的所有细胞创建一系列数字图书馆，其中每个细胞 细胞根据其自身的转录和表观基因组图谱进行注释；2)生成超高密度组织- 下尿路的特定空间转录图谱；以及3)在接近单个的位置显示空间转录组 3D数字化小鼠和人类胚胎上的细胞分辨率。这些资源将为研究服务 社区建立对尿路发育的全面了解，包括但不限于 泄殖腔间隔与尿路分化。

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.