Conserved and Divergent Features of Human and Mouse Kidney Organogenesis
Conserved and Divergent Features of Human and Mouse Kidney Organogenesis
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DOI：
10.1681/asn.2017080887
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发表时间：
2018-03-01
影响因子：
13.6
通讯作者：
McMahon, Andrew P.
中科院分区：
文献类型：
--
作者：
Lindstrom, Nils O.;McMahon, Jill A.;McMahon, Andrew P.
人类肾脏功能由大约1，000，000个肾单位支撑，尽管数量变化很大，并且肾单位数量少与疾病有关。人类肾脏发育开始于妊娠4周左右，结束于妊娠34-37周左右。在此期间，一个反复的诱导过程建立了肾单位补体。研究提供了人类肾脏发育的深刻解剖描述，但有限的组织学观点并不容易为广大观众所接受。在这篇提供对人类肾脏形成的全面了解的系列文章中，我们在135个匿名捐赠的人类肾脏标本中检查了人类肾脏的发育。我们通过组织学分析、RNA原位杂交、免疫荧光研究和转录谱分析，在宏观和细胞水平上记录了肾脏发育，并将人类发育（4-23周）与选定阶段（胚胎第15.5天和出生后第2天）的小鼠发育进行了对比。生成的人类肾脏器官发生的高分辨率组织学交互式图谱可以在GUDMAP数据库（www.gudmap.org）上查看，以及本文数据的关键组成部分的三维重建。在解剖学水平上，人类和小鼠肾脏发育在时间、规模和整体特征（如肺叶形成和祖细胞生态位组织）方面存在差异。这些数据还突出了分子和细胞特征的差异，包括用于识别小鼠肾脏研究中关键细胞类型的锚基因标记物的表达和细胞分布。这些数据将促进和通知在体外的努力，以产生人类肾脏结构和比较功能分析哺乳动物物种。
Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.