@article{a712284864294bc9ad844a0af7c3fa95,
title = "An atlas of healthy and injured cell states and niches in the human kidney",
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.",
author = "{KPMP Consortium} and Lake, {Blue B.} and Rajasree Menon and Seth Winfree and Qiwen Hu and Ferreira, {Ricardo Melo} and Kian Kalhor and Daria Barwinska and Otto, {Edgar A.} and Michael Ferkowicz and Dinh Diep and Nongluk Plongthongkum and Amanda Knoten and Sarah Urata and Mariani, {Laura H.} and Naik, {Abhijit S.} and Sean Eddy and Bo Zhang and Yan Wu and Diane Salamon and Williams, {James C.} and Xin Wang and Balderrama, {Karol S.} and Hoover, {Paul J.} and Evan Murray and Marshall, {Jamie L.} and Teia Noel and Anitha Vijayan and Austin Hartman and Fei Chen and Waikar, {Sushrut S.} and Rosas, {Sylvia E.} and Wilson, {Francis P.} and Palevsky, {Paul M.} and Krzysztof Kiryluk and Sedor, {John R.} and Toto, {Robert D.} and Parikh, {Chirag R.} and Kim, {Eric H.} and Rahul Satija and Anna Greka and Macosko, {Evan Z.} and Kharchenko, {Peter V.} and Gaut, {Joseph P.} and Hodgin, {Jeffrey B.} and Richard Knight and Shweta Bansal and Kumar Sharma and Manjeri Venkatachalam and Guanshi Zhang and Kun Zhang",
note = "Funding Information: We thank the patients who volunteered to donate tissue primarily for research purposes despite no direct immediate benefit to their clinical care; collaborators L. J. Arend, S. M. Bagnasco, C. J. Sperrati and M. Atta for providing samples from patients with COVID-AKI; Y. Yang for his expertise in performing the in situ hybridization experiments; the members of the KPMP nomenclature working group for establishing the nephron schema and standardized nomenclature used, specifically, T. Valerius, W. Kriz, B. Kaissling and M. Rose; the members of the HuBMAP consortium including the HuBMAP HIVE for building the infrastructure for data storage and public access to reference samples, in particular, J. Silverstein, P. Kant, K. Borner and N. Gehlenborg; J. Hilton and J. Yu-Sheng Chien for building the CellxGene instance of the integrated datasets as part of the Chan Zuckerburg Initiative; the staff at the Indiana Center for Biological Microscopy for imaging assistance; the staff at the Indiana Center for Medical Genomics for sequencing of the 10x Visium samples; the staff at the Indiana Biobank for hosting the BBCI; the staff at the Kidney Translational Research Center (KTRC) at the Washington University (Division of Nephrology) and Mid America Transplant in St Louis for infrastructural support for HuBMAP samples; and the S. Steffan family for support of new omics technologies in kidney research (B1401-40 to S.J.). This publication is part of the HCA (https://humancellatlas.org/publications). The snCv3 and SNARE2 sequencing data were generated at the UC San Diego IGM Genomics Center supported by the National Institutes of Health (SIG grant S10 OD026929) and Washington University Genome Technology Access Center at the McDonnell Genome Institute partially supported by NCI Cancer Center Support (P30 CA91842) to the Siteman Cancer Center and by ICTS/CTSA (UL1TR002345) from the National Center for Research Resources (NCRR). The KPMP data presented here were funded by the following grants from the NIDDK: U2C DK114886, UH3DK114861, UH3DK114866, UH3DK114870, UH3DK114908, UH3DK114915, UH3DK114926, UH3DK114907, UH3DK114923 and UH3DK114933. The HuBMAP data presented here were supported by OT2D033760 (to R.S.), U54HL145608 (to S.J. and K.Z.) and U54DK134301 (to S.J.). Additional NIH support was provided by NIH/NIDDK K08DK107864 (to M.T.E.); Indiana Grand Challenge Precision Health fund (to R.M.F.); R01DK111651 (to T.M.E.-A.); P30 DK079312 (to T.M.E.-A. and P.C.D.); P01 DK056788 (to J.C.W.); U2CDK114886, U54DK083912, P30 DK081943/HCA: Kidney Seed Network (to M.K.); K23DK125529 (to A.S.N.); U54DK083912 (to S.E.); U01MH114828 (to K. Kalhor); UH3CA246632 (to E.Z.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank the patients who volunteered to donate tissue primarily for research purposes despite no direct immediate benefit to their clinical care; collaborators L. J. Arend, S. M. Bagnasco, C. J. Sperrati and M. Atta for providing samples from patients with COVID-AKI; Y. Yang for his expertise in performing the in situ hybridization experiments; the members of the KPMP nomenclature working group for establishing the nephron schema and standardized nomenclature used, specifically, T. Valerius, W. Kriz, B. Kaissling and M. Rose; the members of the HuBMAP consortium including the HuBMAP HIVE for building the infrastructure for data storage and public access to reference samples, in particular, J. Silverstein, P. Kant, K. Borner and N. Gehlenborg; J. Hilton and J. Yu-Sheng Chien for building the CellxGene instance of the integrated datasets as part of the Chan Zuckerburg Initiative; the staff at the Indiana Center for Biological Microscopy for imaging assistance; the staff at the Indiana Center for Medical Genomics for sequencing of the 10x Visium samples; the staff at the Indiana Biobank for hosting the BBCI; the staff at the Kidney Translational Research Center (KTRC) at the Washington University (Division of Nephrology) and Mid America Transplant in St Louis for infrastructural support for HuBMAP samples; and the S. Steffan family for support of new omics technologies in kidney research (B1401-40 to S.J.). This publication is part of the HCA ( https://humancellatlas.org/publications ). The snCv3 and SNARE2 sequencing data were generated at the UC San Diego IGM Genomics Center supported by the National Institutes of Health (SIG grant S10 OD026929) and Washington University Genome Technology Access Center at the McDonnell Genome Institute partially supported by NCI Cancer Center Support (P30 CA91842) to the Siteman Cancer Center and by ICTS/CTSA (UL1TR002345) from the National Center for Research Resources (NCRR). The KPMP data presented here were funded by the following grants from the NIDDK: U2C DK114886, UH3DK114861, UH3DK114866, UH3DK114870, UH3DK114908, UH3DK114915, UH3DK114926, UH3DK114907, UH3DK114923 and UH3DK114933. The HuBMAP data presented here were supported by OT2D033760 (to R.S.), U54HL145608 (to S.J. and K.Z.) and U54DK134301 (to S.J.). Additional NIH support was provided by NIH/NIDDK K08DK107864 (to M.T.E.); Indiana Grand Challenge Precision Health fund (to R.M.F.); R01DK111651 (to T.M.E.-A.); P30 DK079312 (to T.M.E.-A. and P.C.D.); P01 DK056788 (to J.C.W.); U2CDK114886, U54DK083912, P30 DK081943/HCA: Kidney Seed Network (to M.K.); K23DK125529 (to A.S.N.); U54DK083912 (to S.E.); U01MH114828 (to K. Kalhor); UH3CA246632 (to E.Z.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = jul,
day = "20",
doi = "10.1038/s41586-023-05769-3",
language = "English (US)",
volume = "619",
pages = "585--594",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7970",
}