Biomedical Research Core

摘要 儿童肾脏生物医学核心(PKidBIO Core) 肾脏疾病是婴幼儿、儿童和青少年的主要疾病和死亡原因。 美国这些患者中终末期肾病(ESKD)的发病率约为15% 每百万人。迅速增加的成人高血压和肾功能衰竭的问题也可能 根植于儿童肾脏的侮辱，没有被发现，没有预防，也没有治疗。最新进展 肾脏早期检测和严重程度测量的有效干预和方法 儿童疾病滞后的部分原因是缺乏生理学和病理学知识。 肾脏成熟时发生的变化。分子蓝图将大大增强我们的 有能力设计有效的方法来干预和预防肾功能障碍。这个目标 然而，如果没有儿科肾脏组织的来源来开始分子治疗，就不能满足 审问，以确定，独特的人类和发展，所需的术语指令 制造和维护健康的肾脏。PKidBIO核心，作为华盛顿大学的一部分 儿科卓越中心，处于异常强大和独特的地位，为 所需的儿童肾脏组织，源自临床活检或作为同意的“生命礼物” 研究，保存的方法被证明与最新的技术兼容 使特定年龄的研究能够挖掘多组单细胞转录组和表观基因组 化验、分子成像和组织工程。根据其设计和性质，pKidBIO核心将 通过以下方式促进儿科肾脏疾病研究的热情和进步：1)提供 胎儿和儿童肾脏疾病组织的特定年龄参考，2)旨在 描述与出生后相关的细胞、形态、生理和分子变化 肾脏成熟，3)加速针对体外人肾有机化合物的科学研究，4) 建立分离分化的肾脏细胞类型的方案，其阶段与 在肾组织样本中可以看到，5)推进了药物毒性筛选，并通过6)设计验证 基因功能和肾脏工程的研究。组织的可获得性和突出的 由它们产生的数据将吸引肾脏研究开发空间之外的新专业知识 对生理性衰老感兴趣的成像和分析技术和研究 寿命。PKidBIO存储库将成为国家研究和临床资源 可查找、可访问、可互操作和可重用的社区。

Abstract Pediatric Kidney BioMedical Core (pKidBIO Core) Kidney disease is a major cause of illness and death in infants, children, and adolescents with the incidence of end-stage kidney disease (ESKD) in these patients in the United States of about 15 per million. The rapidly increasing problems of adult hypertension and renal failure may also have roots in pediatric kidney insults that go undetected, unprevented and untreated. The development of effective interventions and methods of early detection and severity measurements of renal disease in children is lagging in part due to a lack of knowledge of physiological and pathological changes that occur as the kidney matures. Molecular blueprints would dramatically enhance our ability to design effective approaches to intervene and prevent kidney dysfunction. This goal cannot be met, however, without having a source of pediatric kidney tissue to begin molecular interrogations to identify the, uniquely human and developmental, ’omic instructions required to make and maintain healthy kidneys. The pKidBIO core, as part of the Washington University Pediatric Center of Excellence, is in an unusually strong and unique position to provide the required pediatric kidney tissues, originating from clinical biopsies or as “gifts of life” consented for research, preserved with methods shown to be compatible with the most recent technologies to enable age-specific research to dig into multi-omic single cell transcriptome and epigenome assays, molecular imaging and tissue engineering. By its design and nature, the pKidBIO core will promote enthusiasm and progress in pediatric kidney disease research by 1) providing human age-specific references for fetal and childhood kidney disease tissues, 2) enabling studies aimed to delineate cellular, morphological, physiological and molecular changes associated with postnatal kidney maturation, 3) accelerating scientific research aimed at ex vivo human kidney organoids, 4) establishing protocols for isolating differentiated kidney cell types at stages consistent with those seen in kidney tissue samples, 5) advancing drug toxicity screening, and by 6) designing validation studies of gene function and kidney engineering. The availability of the tissue and the outstanding data generated from them will attract new expertise outside kidney research developing spatial imaging and analytical technologies and research interested in physiological aging across the lifespan. The pKidBIO repository will be a national resource for the research and clinical community that is findable, accessible, interoperable, and reusable.