Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

Journal: 
J Am Soc Nephrol
Publication Year: 
2018
Authors: 
Nils O Lindstrom
Jill A McMahon
Jinjin Guo
Tracy Tran
Qiuyu Guo
Elisabeth Rutledge
Riana K Parvez
Gohar Saribekyan
Robert E Schuler
Christopher Liao
Albert D Kim
Ahmed Abdelhalim
Seth W Ruffins
Matthew E Thornton
Laurence Basking
Brendan Grubbs
Carl Kesselman
Andrew P McMahon
PubMed link: 
29449453
Public Summary: 
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. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development at a macroscopic and cellular level. A 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 efforts to generate human kidney structures from stem cells and help in relating findings in the mouse to man.
Scientific Abstract: 
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.