Conserved and divergent features of human and mouse kidney organogenesis

Nils O. Lindström, 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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 viewsare not readily accessible to abroadaudience. 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 andmouse kidney development differ in timing, scale, and global features such as lobe formation andprogenitor 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 inmouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.

Original languageEnglish (US)
Pages (from-to)785-805
Number of pages21
JournalJournal of the American Society of Nephrology
Volume29
Issue number3
DOIs
StatePublished - Mar 2018

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Conserved and divergent features of human and mouse kidney organogenesis'. Together they form a unique fingerprint.

Cite this