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An atlas of healthy and injured cell states and niches in the human kidney

2023; Nature Portfolio; Volume: 619; Issue: 7970 Linguagem: Inglês

10.1038/s41586-023-05769-3

1476-4687

Blue B. Lake, Rajasree Menon, Seth Winfree, Qiwen Hu, Ricardo Melo Ferreira, Kian Kalhor, Daria Barwinska, Edgar A. Otto, Michael J. Ferkowicz, Dinh Diep, Nongluk Plongthongkum, Amanda Knoten, Sarah Urata, Laura H. Mariani, Abhijit S. Naik, Sean Eddy, Bo Zhang, Yan Wu, Diane Salamon, James C. Williams, Xin Wang, Karol S. Balderrama, Paul Hoover, Evan Murray, Jamie L. Marshall, Teia Noel, Anitha Vijayan, Austin Hartman, Fei Chen, Sushrut S. Waikar, Sylvia E. Rosas, F. Perry Wilson, Paul M. Palevsky, Krzysztof Kiryluk, John R. Sedor, Robert D. Toto, Chirag R. Parikh, Eric H. Kim, Rahul Satija, Anna Greka, Evan Z. Macosko, Peter V. Kharchenko, Joseph P. Gaut, Jeffrey B. Hodgin, Richard A. Knight, Stewart H. Lecker, Isaac E. Stillman, Afolarin Amodu, Titlayo Ilori, Shana Maikhor, Insa M. Schmidt, Gearoid M. McMahon, Astrid Weins, Nir Hacohen, Lakeshia Bush, Agustin Gonzalez‐Vicente, Jonathan J. Taliercio, John O’Toole, Emilio D. Poggio, Leslie Cooperman, Stacey E. Jolly, Leal Herlitz, Jane Nguyen, Ellen L. Palmer, Dianna Sendrey, Kassandra Spates-Harden, Paul S. Appelbaum, Jonathan Barasch, Andrew S. Bomback, Vivette D. D’Agati, Karla Mehl, Pietro A. Canetta, Ning Shang, Olivia Balderes, Satoru Kudose, Laura Barisoni, Theodore Alexandrov, Ying‐Hua Cheng, Kenneth W. Dunn, Katherine J. Kelly, Timothy A. Sutton, Yumeng Wen, Celia P. Corona-Villalobos, Steven Menez, Avi Z. Rosenberg, Mohammed Atta, Camille Johansen, Jennifer K. Sun, Neil Roy, Mathew Williams, Evren U. Azeloglu, Cijang He, Ravi Iyengar, Jens Hansen, Yuguang Xiong, Brad H. Rovin, Samir V. Parikh, Sethu M. Madhavan, Christopher Anderton, Ljiljana Paša‐Tolić, Dušan Veličković, Olga G. Troyanskaya, Rachel Sealfon, Katherine R. Tuttle, Zoltán Lászik, Garry P. Nolan, Minnie Sarwal, Kavya Anjani, Tara K. Sigdel, Heather Ascani, Ulysses J. Balis, Chrysta Lienczewski, Becky Steck, Yougqun He, Jennifer A. Schaub, Victoria M. Blanc, Raghavan Murugan, Parmjeet Randhawa, Matthew R. Rosengart, Mitchell Tublin, Tina Vita, John A. Kellum, Daniel E. Hall, Michele Elder, James Winters, Matthew Gilliam, Charles E. Alpers, Kristina N. Blank, Jonas Carson, Ian H. de Boer, Ashveena Dighe, Jonathan Himmelfarb, Sean D. Mooney, Stuart J. Shankland, Kayleen Williams, Chris Park, Frederick Dowd, Robyn L. McClelland, Stephen Daniel, Andrew N. Hoofnagle, Adam B. Wilcox, Shweta Bansal, Kumar Sharma, Manjeri A. Venkatachalam, Guanshi Zhang, Annapurna Pamreddy, Vijaykumar R. Kakade, Dennis G. Moledina, Melissa Shaw, Ugochukwu Ugwuowo, Tanima Arora, Joseph Ardayfio, Jack Bebiak, Keith Brown, Catherine E. Campbell, John Saul, Anna Shpigel, Christy Stutzke, Robert Koewler, Taneisha Campbell, Lynda Hayashi, Nichole Jefferson, Roy Pinkeney, Glenda V. Roberts, Michael T. Eadon, Pierre C. Dagher, Tarek M. El‐Achkar, Kun Zhang, Matthias Kretzler, Sanjay Jain,

Chronic Kidney Disease and Diabetes

Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods 1 . 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.