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

下尿路表观基因组和转录组的单细胞同细胞3D图谱

• 批准号: 10356656
• 负责人: Xue Sean Li
• 金额: $ 46.05万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10356656
• 关键词: 3-Dimensional; Anatomy; Area; Atlases; Birth; Bladder; Case Study; Cell Nucleus; Cells; Cloaca Chamber; Collection; Communities; Complex; Congenital Abnormality; Data; Data Set; Development; Developmental Process; Digital Libraries; Disease; Dorsal; Embryo; Gene Expression Profile; Generations; Genes; Genital; Genitalia; Genitourinary system; Glass; Goals; Graph; Hindgut; Histology; Human; Image; Joints; Life; Location; Lower urinary tract; Maps; Mesenchyme; Molecular; Molecular Profiling; Mus; Organ; Play; Reporting; Research; Resolution; Resources; Role; Series; Signaling Molecule; Slice; Slide; Spottings; Structure; Structure of umbilical artery; Technology; Time; Tissue-Specific Gene Expression; Tissues; Ureter; Urethra; Urinary tract; Vascular System; base; bladder trigone; cell type; density; design; digital; epigenome; epigenomics; improved; innovation; innovative technologies; molecular marker; multiple omics; novel; response; transcription factor; transcriptome; transcriptomics; urogenital tract; virtual; virtual human

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.

回应 RFA-DK-20-013“泌尿生殖发育分子解剖学项目 (GUDMAP) - Atlas 项目”，该提案旨在“生成数据以可视化正在发育的泌尿道，识别新的功能 和解剖结构域，以及细胞类型”。胚胎后肠或泄殖腔是从一个空腔发展而来的。 器官分为两个独立的实体——泌尿道和肛门直肠。 在组织特异性基因表达模式的指导下，我们研究了膀胱吻侧和生殖器尿道尾侧。 研究表明，几种选定的转录因子和信号分子对于尿路发育至关重要 和，导致一些最复杂的人类出生缺陷。然而，这些低通量和。 孤立的案例研究提供的信息有限；并且很难整合这些发现来辨别基因与基因之间的关系； 发育和疾病中的基因-细胞关系，包括所有基因的空间注释。 需要使用单细胞多组学和空间转录组等创新技术。 应用程序的目的是1）从小鼠下尿路的所有细胞创建一系列数字库，其中每个 细胞根据其自身的转录组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组图；3) 显示近单一的空间转录组 细胞分辨率到 3D 数字化小鼠和人类胚胎上，这些资源将为研究服务。 社区建立对泌尿道发育的全面了解，包括但不限于 泄殖腔分隔和尿路分化。