Spatial transcriptional mapping of the human nephrogenic program. Author Nils Lindström, Rachel Sealfon, Xi Chen, Riana Parvez, Andrew Ransick, Guilherme Brandine, Jinjin Guo, Bill Hill, Tracy Tran, Albert Kim, Jian Zhou, Alicja Tadych, Aaron Watters, Aaron Wong, Elizabeth Lovero, Brendan Grubbs, Matthew Thornton, Jill McMahon, Andrew Smith, Seth Ruffins, Chris Armit, Olga Troyanskaya, Andrew McMahon Publication Year 2021 Type Journal Article Abstract Congenital abnormalities of the kidney and urinary tract are among the most common birth defects, affecting 3% of newborns. The human kidney forms around a million nephrons from a pool of nephron progenitors over a 30-week period of development. To establish a framework for human nephrogenesis, we spatially resolved a stereotypical process by which equipotent nephron progenitors generate a nephron anlage, then applied data-driven approaches to construct three-dimensional protein maps on anatomical models of the nephrogenic program. Single-cell RNA sequencing identified progenitor states, which were spatially mapped to the nephron anatomy, enabling the generation of functional gene networks predicting interactions within and between nephron cell types. Network mining identified known developmental disease genes and predicted targets of interest. The spatially resolved nephrogenic program made available through the Human Nephrogenesis Atlas (https://sckidney.flatironinstitute.org/) will facilitate an understanding of kidney development and disease and enhance efforts to generate new kidney structures. Keywords Animals, Mice, Humans, Gene Expression Regulation, Developmental, Proteome, Single-Cell Analysis, Transcriptome, Nephrons, RNA-Seq Journal Dev Cell Volume 56 Issue 16 Pages 2381-2398.e6 Date Published 2021 Aug 23 ISSN Number 1878-1551 DOI 10.1016/j.devcel.2021.07.017 Alternate Journal Dev Cell PMCID PMC8396064 PMID 34428401 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML