1. Publications

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

Blue B. Lake, Rajasree Menon, Seth Winfree, Qiwen Hu, Ricardo Melo Ferreira, Kian Kalhor, Daria Barwinska, Edgar A. Otto, Michael 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 J. Hoover, Evan Murray, Jamie L. Marshall, Teia Noel, Anitha Vijayan, Austin Hartman, Fei Chen, Sushrut S. Waikar, Sylvia E. Rosas, Francis P. 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, KPMP Consortium, Michael T. Eadon, Pierre C. Dagher, Tarek M. El-Achkar, Kun Zhang, Matthias Kretzler & Sanjay Jain.
Nature. 2023-07-19;619(7970):585-594.
Abstract
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.
Datasets
DSR833483