An atlas of healthy and injured cell states and niches in the human kidney
Authors: Lake Blue B. , Menon Rajasree , Winfree Seth , Hu Qiwen , Melo Ferreira Ricardo , Kalhor Kian , Barwinska Daria , Otto Edgar A. , Ferkowicz Michael , Diep Dinh , Plongthongkum Nongluk , Knoten Amanda , Urata Sarah , Mariani Laura H. , Naik Abhijit S. , Eddy Sean , Zhang Bo , Wu Yan , Salamon Diane , Williams James C. , Wang Xin , Balderrama Karol S. , Hoover Paul J. , Murray Evan , Marshall Jamie L. , Noel Teia , Vijayan Anitha , Hartman Austin , Chen Fei , Waikar Sushrut S. , Rosas Sylvia E. , Wilson Francis P. , Palevsky Paul M. , Kiryluk Krzysztof , Sedor John R. , Toto Robert D. , Parikh Chirag R. , Kim Eric H. , Satija Rahul , Greka Anna , Macosko Evan Z. , Kharchenko Peter V. , Gaut Joseph P. , Hodgin Jeffrey B. ,   KPMP Consortium, Knight Richard , Lecker Stewart H. , Stillman Isaac , Amodu Afolarin A. , Ilori Titlayo , Maikhor Shana , Schmidt Insa , McMahon Gearoid M. , Weins Astrid , Hacohen Nir , Bush Lakeshia , Gonzalez-Vicente Agustin , Taliercio Jonathan , O’toole John , Poggio Emilio , Cooperman Leslie , Jolly Stacey , Herlitz Leal , Nguyen Jane , Palmer Ellen , Sendrey Dianna , Spates-Harden Kassandra , Appelbaum Paul , Barasch Jonathan M. , Bomback Andrew S. , D’Agati Vivette D. , Mehl Karla , Canetta Pietro A. , Shang Ning , Balderes Olivia , Kudose Satoru , Barisoni Laura , Alexandrov Theodore , Cheng Yinghua , Dunn Kenneth W. , Kelly Katherine J. , Sutton Timothy A. , Wen Yumeng , Corona-Villalobos Celia P. , Menez Steven , Rosenberg Avi , Atta Mohammed , Johansen Camille , Sun Jennifer , Roy Neil , Williams Mark , Azeloglu Evren U. , He Cijang , Iyengar Ravi , Hansen Jens , Xiong Yuguang , Rovin Brad , Parikh Samir , Madhavan Sethu M. , Anderton Christopher R. , Pasa-Tolic Ljiljana , Velickovic Dusan , Troyanskaya Olga , Sealfon Rachel , Tuttle Katherine R. , Laszik Zoltan G. , Nolan Garry , Sarwal Minnie , Anjani Kavya , Sigdel Tara , Ascani Heather , Balis Ulysses G. J. , Lienczewski Chrysta , Steck Becky , He Yougqun , Schaub Jennifer , Blanc Victoria M. , Murugan Raghavan , Randhawa Parmjeet , Rosengart Matthew , Tublin Mitchell , Vita Tina , Kellum John A. , Hall Daniel E. , Elder Michele M. , Winters James , Gilliam Matthew , Alpers Charles E. , Blank Kristina N. , Carson Jonas , De Boer Ian H. , Dighe Ashveena L. , Himmelfarb Jonathan , Mooney Sean D. , Shankland Stuart , Williams Kayleen , Park Christopher , Dowd Frederick , McClelland Robyn L. , Daniel Stephen , Hoofnagle Andrew N. , Wilcox Adam , Bansal Shweta , Sharma Kumar , Venkatachalam Manjeri , Zhang Guanshi , Pamreddy Annapurna , Kakade Vijaykumar R. , Moledina Dennis , Shaw Melissa M. , Ugwuowo Ugochukwu , Arora Tanima , Ardayfio Joseph , Bebiak Jack , Brown Keith , Campbell Catherine E. , Saul John , Shpigel Anna , Stutzke Christy , Koewler Robert , Campbell Taneisha , Hayashi Lynda , Jefferson Nichole , Pinkeney Roy , Roberts Glenda V. , Eadon Michael T. , Dagher Pierre C. , El-Achkar Tarek M. , Zhang Kun , Kretzler Matthias , Jain Sanjay 
Published: July 2023

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. 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.