Spatial transcriptional mapping of the human nephrogenic program.

TitleSpatial transcriptional mapping of the human nephrogenic program.
Publication TypeJournal Article
Year of Publication2021
AuthorsLindström, NO, Sealfon, R, Chen, X, Parvez, RK, Ransick, A, Brandine, GDe Sena, Guo, J, Hill, B, Tran, T, Kim, AD, Zhou, J, Tadych, A, Watters, A, Wong, A, Lovero, E, Grubbs, BH, Thornton, ME, McMahon, JA, Smith, AD, Ruffins, SW, Armit, C, Troyanskaya, OG, McMahon, AP
JournalDev Cell
Volume56
Issue16
Pagination2381-2398.e6
Date Published2021/08/23
ISSN1878-1551
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.

DOI10.1016/j.devcel.2021.07.017
Alternate JournalDev Cell
PubMed ID34428401
PubMed Central IDPMC8396064
Grant ListU24 DK100845 / DK / NIDDK NIH HHS / United States
U01 DK094526 / DK / NIDDK NIH HHS / United States
U01 DK107350 / DK / NIDDK NIH HHS / United States
R01 DK054364 / DK / NIDDK NIH HHS / United States
U01 DK110792 / DK / NIDDK NIH HHS / United States
U2C DK114886 / DK / NIDDK NIH HHS / United States
UH3 TR002158 / TR / NCATS NIH HHS / United States