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

View ORCID ProfileBlue B. Lake, View ORCID ProfileRajasree Menon, View ORCID ProfileSeth Winfree, View ORCID ProfileQiwen Hu, View ORCID ProfileRicardo Melo Ferreira, View ORCID ProfileKian Kalhor, View ORCID ProfileDaria Barwinska, View ORCID ProfileEdgar A. Otto, Michael Ferkowicz, View ORCID ProfileDinh Diep, View ORCID ProfileNongluk Plongthongkum, View ORCID ProfileAmanda Knoten, Sarah Urata, Abhijit S. Naik, View ORCID ProfileSean Eddy, Bo Zhang, Yan Wu, View ORCID ProfileDiane Salamon, James C. Williams, View ORCID ProfileXin Wang, View ORCID ProfileKarol S. Balderrama, Paul Hoover, View ORCID ProfileEvan Murray, Anitha Vijayan, View ORCID ProfileFei Chen, View ORCID ProfileSushrut S. Waikar, View ORCID ProfileSylvia Rosas, Francis P. Wilson, View ORCID ProfilePaul M. Palevsky, View ORCID ProfileKrzysztof Kiryluk, View ORCID ProfileJohn R. Sedor, Robert D. Toto, Chirag Parikh, Eric H. Kim, View ORCID ProfileEvan Z. Macosko, View ORCID ProfilePeter V. Kharchenko, View ORCID ProfileJoseph P. Gaut, Jeffrey B. Hodgin, View ORCID ProfileMichael T. Eadon, View ORCID ProfilePierre C. Dagher, View ORCID ProfileTarek M. El-Achkar, View ORCID ProfileKun Zhang, View ORCID ProfileMatthias Kretzler, View ORCID ProfileSanjay Jain, for the KPMP consortium
doi: https://doi.org/10.1101/2021.07.28.454201
Blue B. Lake
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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Rajasree Menon
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
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Seth Winfree
3Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
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Qiwen Hu
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
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Ricardo Melo Ferreira
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Kian Kalhor
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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Daria Barwinska
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Edgar A. Otto
6Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA
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Michael Ferkowicz
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Dinh Diep
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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Nongluk Plongthongkum
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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Amanda Knoten
7Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Sarah Urata
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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Abhijit S. Naik
6Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA
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Sean Eddy
6Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA
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  • ORCID record for Sean Eddy
Bo Zhang
7Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Yan Wu
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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Diane Salamon
7Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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James C. Williams
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Xin Wang
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
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Karol S. Balderrama
8Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
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Paul Hoover
8Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
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Evan Murray
8Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
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Anitha Vijayan
7Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Fei Chen
8Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
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Sushrut S. Waikar
9Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA
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Sylvia Rosas
10Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA
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Francis P. Wilson
11Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
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Paul M. Palevsky
12Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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Krzysztof Kiryluk
13Department of Medicine, Columbia University, New York, NY 10032, USA
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John R. Sedor
14Lerner Research and Glickman Urology and Kidney Institutes, Cleveland Clinic, Cleveland, OH 44195, USA
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Robert D. Toto
15Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
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Chirag Parikh
16Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
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Eric H. Kim
17Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA
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Evan Z. Macosko
8Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
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Peter V. Kharchenko
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
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Joseph P. Gaut
18Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
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Jeffrey B. Hodgin
6Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA
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Michael T. Eadon
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Pierre C. Dagher
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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  • For correspondence: sanjayjain@wustl.edu kretzler@med.umich.edu kzhang@bioeng.ucsd.edu telachka@iu.edu pdaghe2@iu.edu
Tarek M. El-Achkar
5Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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  • For correspondence: sanjayjain@wustl.edu kretzler@med.umich.edu kzhang@bioeng.ucsd.edu telachka@iu.edu pdaghe2@iu.edu
Kun Zhang
1Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
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  • For correspondence: sanjayjain@wustl.edu kretzler@med.umich.edu kzhang@bioeng.ucsd.edu telachka@iu.edu pdaghe2@iu.edu
Matthias Kretzler
6Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA
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  • For correspondence: sanjayjain@wustl.edu kretzler@med.umich.edu kzhang@bioeng.ucsd.edu telachka@iu.edu pdaghe2@iu.edu
Sanjay Jain
7Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
18Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
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  • For correspondence: sanjayjain@wustl.edu kretzler@med.umich.edu kzhang@bioeng.ucsd.edu telachka@iu.edu pdaghe2@iu.edu
19Kidney Research Institute, University of Washington, Seattle, WA 98104, USA
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Abstract

Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. 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. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. 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. 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. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://portal.hubmapconsortium.org/

  • https://atlas.kpmp.org

  • https://azimuth.hubmapconsortium.org/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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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, Abhijit S. Naik, Sean Eddy, Bo Zhang, Yan Wu, Diane Salamon, James C. Williams, Xin Wang, Karol S. Balderrama, Paul Hoover, Evan Murray, Anitha Vijayan, Fei Chen, Sushrut S. Waikar, Sylvia Rosas, Francis P. Wilson, Paul M. Palevsky, Krzysztof Kiryluk, John R. Sedor, Robert D. Toto, Chirag Parikh, Eric H. Kim, 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, Sanjay Jain, for the KPMP consortium
bioRxiv 2021.07.28.454201; doi: https://doi.org/10.1101/2021.07.28.454201
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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, Abhijit S. Naik, Sean Eddy, Bo Zhang, Yan Wu, Diane Salamon, James C. Williams, Xin Wang, Karol S. Balderrama, Paul Hoover, Evan Murray, Anitha Vijayan, Fei Chen, Sushrut S. Waikar, Sylvia Rosas, Francis P. Wilson, Paul M. Palevsky, Krzysztof Kiryluk, John R. Sedor, Robert D. Toto, Chirag Parikh, Eric H. Kim, 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, Sanjay Jain, for the KPMP consortium
bioRxiv 2021.07.28.454201; doi: https://doi.org/10.1101/2021.07.28.454201

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