After injury, there are dynamic acute and chronic morphological and cellular changes in renal tubules and surrounding interstitial niche. This organ system has a remarkable ability to perform its functions by adapting to a wide range of physiological demands and pathological insults. The human kidneys play vital systemic roles in the preservation of body fluid homeostasis, metabolic waste product removal and blood pressure maintenance. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies. These analyses further defined biological pathways relevant to injury niches, including signatures underlying the transition from reference to predicted maladaptive states that were associated with a decline in kidney function during chronic kidney disease. Molecular signatures of these states permitted their localization within injury neighborhoods using spatial transcriptomics, and large-scale 3D imaging analysis of ∼1.2 million neighborhoods provided linkages to active immune responses. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (n = 42) and disease (n = 42) kidneys. Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. El-Achkar, View ORCID Profile Kun Zhang, View ORCID Profile Matthias Kretzler, View ORCID Profile Sanjay Jain, for the KPMP consortium
Palevsky, View ORCID Profile Krzysztof Kiryluk, View ORCID Profile John R. Waikar, View ORCID Profile Sylvia Rosas, Francis P. Balderrama, Paul Hoover, View ORCID Profile Evan Murray, Anitha Vijayan, View ORCID Profile Fei Chen, View ORCID Profile Sushrut S. Williams, View ORCID Profile Xin Wang, View ORCID Profile Karol S. Naik, View ORCID Profile Sean Eddy, Bo Zhang, Yan Wu, View ORCID Profile Diane Salamon, James C. Otto, Michael Ferkowicz, View ORCID Profile Dinh Diep, View ORCID Profile Nongluk Plongthongkum, View ORCID Profile Amanda Knoten, Sarah Urata, Abhijit S.
Lake, View ORCID Profile Rajasree Menon, View ORCID Profile Seth Winfree, View ORCID Profile Qiwen Hu, View ORCID Profile Ricardo Melo Ferreira, View ORCID Profile Kian Kalhor, View ORCID Profile Daria Barwinska, View ORCID Profile Edgar A.
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