A reference tissue atlas for the human kidney-Reference-Cited by-同舟云学术

A reference tissue atlas for the human kidney

Published:2022-06-10 Issue:23 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Hansen Jens¹^ORCID,Sealfon Rachel²³^ORCID,Menon Rajasree⁴^ORCID,Eadon Michael T.⁵^ORCID,Lake Blue B.⁶^ORCID,Steck Becky⁴^ORCID,Anjani Kavya⁷,Parikh Samir⁸,Sigdel Tara K.⁷^ORCID,Zhang Guanshi⁹^ORCID,Velickovic Dusan¹⁰^ORCID,Barwinska Daria⁵^ORCID,Alexandrov Theodore¹¹^ORCID,Dobi Dejan⁷^ORCID,Rashmi Priyanka⁷,Otto Edgar A.⁴^ORCID,Rivera Miguel⁷^ORCID,Rose Michael P.⁴^ORCID,Anderton Christopher R.⁹¹⁰^ORCID,Shapiro John P.⁸^ORCID,Pamreddy Annapurna⁹^ORCID,Winfree Seth⁵^ORCID,Xiong Yuguang¹^ORCID,He Yongqun⁴^ORCID,de Boer Ian H.¹²^ORCID,Hodgin Jeffrey B.⁴^ORCID,Barisoni Laura¹³^ORCID,Naik Abhijit S.⁴^ORCID,Sharma Kumar⁹^ORCID,Sarwal Minnie M.⁷^ORCID,Zhang Kun⁶^ORCID,Himmelfarb Jonathan¹²,Rovin Brad⁸^ORCID,El-Achkar Tarek M.⁵^ORCID,Laszik Zoltan⁷^ORCID,He John Cijiang¹^ORCID,Dagher Pierre C.⁵^ORCID,Valerius M. Todd¹⁴^ORCID,Jain Sanjay¹⁵^ORCID,Satlin Lisa M.¹,Troyanskaya Olga G.²³^ORCID,Kretzler Matthias⁴^ORCID,Iyengar Ravi¹^ORCID,Azeloglu Evren U.¹^ORCID,

Affiliation:

1. Icahn School of Medicine at Mount Sinai, New York, NY, USA.

2. Princeton University, Princeton, NJ, USA.

3. Flatiron Institute, New York, NY, USA.

4. University of Michigan School of Medicine, Ann Arbor, MI, USA .

5. Indiana University School of Medicine, Indianapolis, IN, USA.

6. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.

7. University of California San Francisco School of Medicine, San Francisco, CA, USA.

8. Ohio State University College of Medicine, Columbus, OH, USA.

9. University of Texas–Health San Antonio School of Medicine, San Antonio, TX, USA.

10. Pacific Northwest National Laboratory, Richland, WA, USA.

11. European Molecular Biology Laboratory, Heidelberg, Germany.

12. Schools of Medicine and Public Health, University of Washington, Seattle, WA, USA.

13. Duke University School of Medicine, Durham, NC, USA.

14. Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA.

15. Washington University in Saint Louis School of Medicine, St. Louis, MS, USA.

Abstract

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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