An atlas of healthy and injured cell states and niches in the human kidney
Blue B. Lake(Fleet Science Center), Rajasree Menon(University of Michigan), Seth Winfree(University of Nebraska Medical Center), Qiwen Hu(Harvard University), Ricardo Melo Ferreira(Indiana University School of Medicine), Kian Kalhor(University of California San Diego), Daria Barwinska(Indiana University School of Medicine), Edgar A. Otto(University of Michigan), Michael J. Ferkowicz(Indiana University School of Medicine), Dinh Diep(Fleet Science Center), Nongluk Plongthongkum(University of California San Diego), Amanda Knoten(Washington University in St. Louis), Sarah Urata(University of California San Diego), Laura H. Mariani(University of Michigan), Abhijit S. Naik(University of Michigan), Sean Eddy(University of Michigan), Bo Zhang(Washington University in St. Louis), Yan Wu(Fleet Science Center), Diane Salamon(Washington University in St. Louis), James C. Williams(Indiana University School of Medicine), Xin Wang(Harvard University), Karol S. Balderrama(Broad Institute), Paul Hoover(Broad Institute), Evan Murray(Broad Institute), Jamie L. Marshall(Broad Institute), Teia Noel(Broad Institute), Anitha Vijayan(Washington University in St. Louis), Austin Hartman(New York Genome Center), Fei Chen(Broad Institute), Sushrut S. Waikar(Boston University), Sylvia E. Rosas(Joslin Diabetes Center), F. Perry Wilson(Yale University), Paul M. Palevsky(University of Pittsburgh), Krzysztof Kiryluk(Columbia University), John R. Sedor(Cleveland Clinic), Robert D. Toto(Southwestern Medical Center), Chirag R. Parikh(Johns Hopkins University), Eric H. Kim(Washington University in St. Louis), Rahul Satija(New York Genome Center), Anna Greka(Broad Institute), Evan Z. Macosko(Broad Institute), Peter V. Kharchenko(Fleet Science Center), Joseph P. Gaut(Washington University in St. Louis), Jeffrey B. Hodgin(University of Michigan), Richard A. Knight(American Association of Kidney Patients), Stewart H. Lecker(Beth Israel Deaconess Medical Center), Isaac E. Stillman(Beth Israel Deaconess Medical Center), Afolarin Amodu(Boston University), Titlayo Ilori(Boston University), Shana Maikhor(Boston University), Insa M. Schmidt(Boston University), Gearoid M. McMahon(Brigham and Women's Hospital), Astrid Weins(Brigham and Women's Hospital), Nir Hacohen(Broad Institute), Lakeshia Bush(Cleveland Clinic), Agustin Gonzalez‐Vicente(Cleveland Clinic), Jonathan J. Taliercio(Cleveland Clinic), John O’Toole(Cleveland Clinic), Emilio D. Poggio(Cleveland Clinic), Leslie Cooperman(Cleveland Clinic), Stacey E. Jolly(Cleveland Clinic), Leal Herlitz(Cleveland Clinic), Jane Nguyen(Cleveland Clinic), Ellen L. Palmer(Cleveland Clinic), Dianna Sendrey(Cleveland Clinic), Kassandra Spates-Harden(Cleveland Clinic), Paul S. Appelbaum(Columbia University), Jonathan Barasch(Columbia University), Andrew S. Bomback(Columbia University), Vivette D. D’Agati(Columbia University), Karla Mehl(Columbia University), Pietro A. Canetta(Columbia University), Ning Shang(Columbia University), Olivia Balderes(Columbia University), Satoru Kudose(Columbia University), Laura Barisoni(Duke University), Theodore Alexandrov(European Molecular Biology Laboratory), Ying‐Hua Cheng(Indiana University School of Medicine), Kenneth W. Dunn(Indiana University School of Medicine), Katherine J. Kelly(Indiana University School of Medicine), Timothy A. Sutton(Indiana University School of Medicine), Yumeng Wen(Johns Hopkins University), Celia P. Corona-Villalobos(Johns Hopkins University), Steven Menez(Johns Hopkins University), Avi Z. Rosenberg(Johns Hopkins University), Mohammed Atta(Johns Hopkins University), Camille Johansen(Joslin Diabetes Center), Jennifer K. Sun(Joslin Diabetes Center), Neil Roy(Joslin Diabetes Center), Mark Williams(Joslin Diabetes Center), Evren U. Azeloglu(Icahn School of Medicine at Mount Sinai), Cijang He(Icahn School of Medicine at Mount Sinai), Ravi Iyengar(Icahn School of Medicine at Mount Sinai), Jens Hansen(Icahn School of Medicine at Mount Sinai), Yuguang Xiong(Icahn School of Medicine at Mount Sinai), Brad H. Rovin(The Ohio State University), Samir V. Parikh(The Ohio State University), Sethu M. Madhavan(The Ohio State University), Christopher Anderton(Pacific Northwest National Laboratory), Ljiljana Paša‐Tolić(Pacific Northwest National Laboratory), Dušan Veličković(Pacific Northwest National Laboratory), Olga G. Troyanskaya(Princeton University), Rachel Sealfon(Princeton University), Katherine R. Tuttle(Providence Health & Services), Zoltán Lászik(University of California, San Francisco), Garry P. Nolan(Stanford University), Minnie Sarwal(University of California, San Francisco), Kavya Anjani(University of California, San Francisco), Tara K. Sigdel(University of California, San Francisco), Heather Ascani(University of Michigan), Ulysses J. Balis(University of Michigan), Chrysta Lienczewski(University of Michigan), Becky Steck(University of Michigan), Yougqun He(University of Michigan), Jennifer A. Schaub(University of Michigan), Victoria M. Blanc(University of Michigan), Raghavan Murugan(University of Pittsburgh), Parmjeet Randhawa(University of Pittsburgh), Matthew R. Rosengart(University of Pittsburgh), Mitchell Tublin(University of Pittsburgh), Tina Vita(University of Pittsburgh), John A. Kellum(University of Pittsburgh), Daniel E. Hall(University of Pittsburgh), Michele Elder(University of Pittsburgh), James Winters(University of Pittsburgh), Matthew Gilliam(University of Pittsburgh), Charles E. Alpers(University of Washington), Kristina N. Blank(University of Washington), Jonas Carson(University of Washington), Ian H. de Boer(University of Washington), Ashveena Dighe(University of Washington), Jonathan Himmelfarb(University of Washington), Sean D. Mooney(University of Washington), Stuart J. Shankland(University of Washington), Kayleen Williams(University of Washington), Chris Park(University of Washington), Frederick Dowd(University of Washington), Robyn L. McClelland(University of Washington), Stephen Daniel(University of Washington), Andrew N. Hoofnagle(University of Washington), Adam Wilcox(University of Washington), Shweta Bansal(The University of Texas at San Antonio Health Science Center), Kumar Sharma(The University of Texas at San Antonio Health Science Center), Manjeri A. Venkatachalam(The University of Texas at San Antonio Health Science Center), Guanshi Zhang(The University of Texas at San Antonio Health Science Center), Annapurna Pamreddy(The University of Texas at San Antonio Health Science Center), Vijaykumar R. Kakade(Yale University), Dennis G. Moledina(Yale University), Melissa Shaw(Yale University), Ugochukwu Ugwuowo(Yale University), Tanima Arora(Yale University), Joseph Ardayfio(Yale University), Jack Bebiak, Keith Brown, Catherine E. Campbell, John Saul(University of Pittsburgh), Anna Shpigel(The University of Texas at San Antonio Health Science Center), Christy Stutzke, Robert Koewler(Southwestern Medical Center), Taneisha Campbell, Lynda Hayashi, Nichole Jefferson, Roy Pinkeney(Princeton University), Glenda V. Roberts, Michael T. Eadon(Indiana University School of Medicine), Pierre C. Dagher(Indiana University School of Medicine), Tarek M. El‐Achkar(Indiana University School of Medicine), Kun Zhang(Fleet Science Center), Matthias Kretzler(University of Michigan), Sanjay Jain(Washington University in St. Louis)
Cited by 634Open Access
Abstract
. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.
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