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, Michael T. Eadon (), Pierre C. Dagher (), Tarek M. El-Achkar (), Kun Zhang (), Matthias Kretzler () and Sanjay Jain ()
Additional contact information
Blue B. Lake: University of California, San Diego
Rajasree Menon: University of Michigan
Seth Winfree: University of Nebraska Medical Center
Qiwen Hu: Harvard Medical School
Ricardo Melo Ferreira: Indiana University School of Medicine
Kian Kalhor: University of California, San Diego
Daria Barwinska: Indiana University School of Medicine
Edgar A. Otto: University of Michigan
Michael Ferkowicz: Indiana University School of Medicine
Dinh Diep: University of California, San Diego
Nongluk Plongthongkum: University of California, San Diego
Amanda Knoten: Washington University School of Medicine
Sarah Urata: University of California, San Diego
Laura H. Mariani: University of Michigan
Abhijit S. Naik: University of Michigan
Sean Eddy: University of Michigan
Bo Zhang: Washington University School of Medicine
Yan Wu: University of California, San Diego
Diane Salamon: Washington University School of Medicine
James C. Williams: Indiana University School of Medicine
Xin Wang: Harvard Medical School
Karol S. Balderrama: Broad Institute of Harvard and MIT
Paul J. Hoover: Broad Institute of Harvard and MIT
Evan Murray: Broad Institute of Harvard and MIT
Jamie L. Marshall: Broad Institute of Harvard and MIT
Teia Noel: Broad Institute of Harvard and MIT
Anitha Vijayan: Washington University School of Medicine
Austin Hartman: New York Genome Center
Fei Chen: Broad Institute of Harvard and MIT
Sushrut S. Waikar: Boston University School of Medicine and Boston Medical Center
Sylvia E. Rosas: Joslin Diabetes Center
Francis P. Wilson: Yale University School of Medicine
Paul M. Palevsky: University of Pittsburgh School of Medicine
Krzysztof Kiryluk: Columbia University
John R. Sedor: Lerner Research and Glickman Urology and Kidney Institutes, Cleveland Clinic
Robert D. Toto: UT Southwestern Medical Center
Chirag R. Parikh: Johns Hopkins School of Medicine
Eric H. Kim: Washington University School of Medicine
Rahul Satija: New York Genome Center
Anna Greka: Broad Institute of Harvard and MIT
Evan Z. Macosko: Broad Institute of Harvard and MIT
Peter V. Kharchenko: Harvard Medical School
Joseph P. Gaut: Washington University School of Medicine
Jeffrey B. Hodgin: University of Michigan
Michael T. Eadon: Indiana University School of Medicine
Pierre C. Dagher: Indiana University School of Medicine
Tarek M. El-Achkar: Indiana University School of Medicine
Kun Zhang: University of California, San Diego
Matthias Kretzler: University of Michigan
Sanjay Jain: Washington University School of Medicine

Nature, 2023, vol. 619, issue 7970, 585-594

Abstract: 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.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (16)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-05769-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:619:y:2023:i:7970:d:10.1038_s41586-023-05769-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-05769-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().