Title | Spatial transcriptional mapping of the human nephrogenic program. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Lindström, 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 |
Journal | Dev Cell |
Volume | 56 |
Issue | 16 |
Pagination | 2381-2398.e6 |
Date Published | 2021 08 23 |
ISSN | 1878-1551 |
Keywords | Animals, Gene Expression Regulation, Developmental, Humans, Mice, Nephrons, Proteome, RNA-Seq, Single-Cell Analysis, Transcriptome |
Abstract | <p>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.</p> |
DOI | 10.1016/j.devcel.2021.07.017 |
Alternate Journal | Dev Cell |
PubMed ID | 34428401 |
PubMed Central ID | PMC8396064 |
Grant List | U24 DK100845 / DK / NIDDK NIH HHS / United States T32 HD060549 / HD / NICHD 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 |