@article{a0396f739af04a6e8e2bda153386441e,
title = "Spatial transcriptional mapping of the human nephrogenic program",
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 = "disease, human, kidney, machine-learning, nephrogenesis, nephron, networks, registration, single-cell, spatial",
author = "Lindstr{\"o}m, {Nils O.} and Rachel Sealfon and Xi Chen and Parvez, {Riana K.} and Andrew Ransick and {De Sena Brandine}, Guilherme and Jinjin Guo and Bill Hill and Tracy Tran and Kim, {Albert D.} and Jian Zhou and Alicja Tadych and Aaron Watters and Aaron Wong and Elizabeth Lovero and Grubbs, {Brendan H.} and Thornton, {Matthew E.} and McMahon, {Jill A.} and Smith, {Andrew D.} and Ruffins, {Seth W.} and Chris Armit and Troyanskaya, {Olga G.} and McMahon, {Andrew P.}",
note = "Funding Information: We thank current and past members of the McMahon Lab for helpful discussions and feedback. We would also like to thank Melissa L. Wilson (Department of Preventive Medicine, University of Southern California) and Family Planning Associates for coordinating fetal tissue collection. B.H. and C.A. wish to thank Richard Baldock of the MRC Human Genetics Unit, IGMM, University of Edinburgh for supporting this project and providing financial support enabling travel for C.A. to visit USC and N.O.L. at the outset of the project. We thank Friedhelm Hildebrandt for discussion and informational sources on known KD/CAKUT genes and Pietro Cippa for helpful discussions on GWAS studies. Funding: Work in A.P.M.{\textquoteright}s laboratory was supported by grants from the National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( DK054364 , DK110792 ) and the California Institute for Regenerative Medicine ( LA1-06536 ). Work in OT{\textquoteright}s laboratory was supported by NIH/ NIDDK grants U24DK100845 , UGDK114907 , and U2CDK114886 and NIH grant UH3TR002158 to O.G.T. O.G.T. is a senior fellow of the Genetic Networks program of the Canadian Institute for Advanced Research (CIFAR). Funding Information: We thank current and past members of the McMahon Lab for helpful discussions and feedback. We would also like to thank Melissa L. Wilson (Department of Preventive Medicine, University of Southern California) and Family Planning Associates for coordinating fetal tissue collection. B.H. and C.A. wish to thank Richard Baldock of the MRC Human Genetics Unit, IGMM, University of Edinburgh for supporting this project and providing financial support enabling travel for C.A. to visit USC and N.O.L. at the outset of the project. We thank Friedhelm Hildebrandt for discussion and informational sources on known KD/CAKUT genes and Pietro Cippa for helpful discussions on GWAS studies. Funding: Work in A.P.M.?s laboratory was supported by grants from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK054364, DK110792) and the California Institute for Regenerative Medicine (LA1-06536). Work in OT's laboratory was supported by NIH/NIDDK grants U24DK100845, UGDK114907, and U2CDK114886 and NIH grant UH3TR002158 to O.G.T. O.G.T. is a senior fellow of the Genetic Networks program of the Canadian Institute for Advanced Research (CIFAR). N.O.L. R.S. X.C. C.A. O.G.T. and A.P.M. wrote the manuscript. N.O.L. R.S. X.C. C.A. B.H. A.S. O.G.T. and A.P.M. designed the experiments. N.O.L. R.S. X.C. R.P. A.R. G.D.S.B. B.H. J.C. T.T. A. Watters, A. Wong, B.G. M.T. J.A. and S.R. performed experiments and analyses and helped with computational tools and web resources. A.P.M. is a scientific advisor on kidney research at Novartis, TRESTLE Therapeutics, eGENESIS, and IVIVA Medical. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "23",
doi = "10.1016/j.devcel.2021.07.017",
language = "English (US)",
volume = "56",
pages = "2381--2398.e6",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "16",
}