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High resolution transcriptome and gene regulatory mapping of human ureter and bladder across the lifespan

人类输尿管和膀胱整个生命周期的高分辨率转录组和基因调控图谱

基本信息

批准号：
10491331
负责人：
Byron H Lee
金额：
$ 48.3万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
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/10491331
关键词：
Adolescent Adult Affect Age Agreement Algorithmic Analysis Anatomy Area Atlases Bacteria Benign Benign Prostatic Hypertrophy Biological Assay Bladder Bladder Tissue Cell Count Cell Survival Cells Characteristics Childhood Chromatin Collaborations Communities Consent Data Data Analyses Data Set Development Disadvantaged Disease Elderly Family Functional disorder Gender Gene Expression Gene Expression Profile Generations Genitourinary system Genomics Goals Health Expenditures Healthcare Histologic Hospitals Human Immunofluorescence Immunologic Individual Institutional Review Boards Interstitial Cystitis Life Location Longevity Lower urinary tract Maps Messenger RNA Molecular Nonprofit Organizations Normal tissue morphology Ohio Operative Surgical Procedures Organ Organ Donor Organ Procurements Pathologic Pathway interactions Patients Pharmacology Physiological Procedures Process Protein Isoforms Recovery Regulator Genes Research Resolution Resources Site Specific qualifier value Structure System Technology Time Tissue Procurements Tissues Transplantation Transposase Ureter Urethra Urethral Stricture Urinary Incontinence Urinary tract infection Urologic Diseases Viral age group analysis pipeline base care burden cell type cost data hub experience gene regulatory network human tissue insight microbiome novel novel marker novel therapeutics organ regeneration organ repair prevent reconstruction recruit repaired response sex single-cell RNA sequencing tissue processing transcription factor transcriptome transcriptomics urinary urinary bladder neck

项目摘要

Abstract Benign urologic diseases of the lower urinary tract such as urinary tract infections, benign prostatic hyperplasia, voiding dysfunction, urinary incontinence, interstitial cystitis, painful bladder syndrome, and urethral strictures incur significant health care burden in the US. Our lack of a comprehensive molecular and cellular understanding of these tissues in the normal and disease states has directly hindered the development of effective novel therapies for these conditions. We are proposing to generate high-resolution transcriptome and gene regulatory data set for healthy human ureter and bladder tissues across the lifespan in both sexes. The overall goal is to construct a highly integrated cellular and molecular anatomical map of the ureter and bladder in humans. This will enable us to comprehensively understand the cellular composition and lineage relationships of the lower urinary tract system. Towards this aim, we have established a robust tissue procurement and processing workflow. This allows us to recover the lower urinary track en bloc from deceased organ donors and process them, with high cell viability and tissue integrity, for molecular assays. We propose to collect scRNA-seq and Visium spatial transcriptomics data on organ donors in 3 age groups that reflect distinct physiological states in terms of lower urinary tract functions across the human life span. For each donor, we will analyze five specified anatomic locations, lower ureter, dome, ureteral orifice, bladder neck, and urethra, to comprehensively characterize parts of the lower urinary tract that have unique tissues structures and functions. We will use these data to understand the lineage relationships between the different cell types and validate novel markers for each novel cell type by immunostaining. Finally, we will perform scATAC-seq on the most informative tissue locations to gain further insight into the underlying gene regulatory networks. Together these studies will provide, for the first time, a comprehensive analysis of the human bladder and ureter throughout life. These molecular data will become a valuable resource to the research community and ultimately, support efforts in organ repair and regeneration.

摘要