Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules
The organizational principles of nephronal segments are based on anatomical and physiological attributes that are linked to the homeostatic functions of the kidney. Recent molecular approaches have uncovered layers of deeper signatures and states in tubular cells that arise at various time points on the disease trajectory. Here, we introduce an analytical pipeline of multiplexed spatial protein imaging integrated with RNA expression to characterize proximal tubular subpopulations and neighborhoods in human kidney tissue. We demonstrate that, in reference tissue, a large proportion of S1 proximal tubular epithelial cells expresses thymus antigen 1 (THY1), a mesenchymal stromal and stem cell marker that regulates differentiation. Kidney disease is associated with loss of THY1 and transition toward expression of prominin 1 (PROM1), another stem cell marker recently linked to failed repair. Our data support a model in which the interplay between THY1 and PROM1 expression in proximal tubules associates with their regenerative potential and marks the timeline of disease progression.
Authors
- William S. Bowen (ORCID: https://orcid.org/0009-0005-1408-596X)
- Connor J. Gulbronson (ORCID: https://orcid.org/0000-0002-2977-7185)
- Carrie L. Phillips (ORCID: https://orcid.org/0000-0002-0256-0736)
- Seth Winfree (ORCID: https://orcid.org/0000-0002-2396-5871)
- James C. Williams (ORCID: https://orcid.org/0000-0001-6665-6596)
- Debora L. Gisch (ORCID: https://orcid.org/0000-0001-9087-4585)
- Ricardo Melo Ferreira (ORCID: https://orcid.org/0000-0003-2063-9744)
- Paul M. Palevsky (ORCID: https://orcid.org/0000-0002-7334-5400)
- Ian H. de Boer (ORCID: https://orcid.org/0000-0003-1571-7592)
- Mahla Asghari (ORCID: https://orcid.org/0000-0003-3907-6267)
- Katherine J. Kelly (ORCID: https://orcid.org/0000-0001-7244-9657)
- Chirag R. Parikh (ORCID: https://orcid.org/0000-0001-9051-7385)
- Pinaki Sarder (ORCID: https://orcid.org/0000-0003-2450-5233)
- Krzysztof Kiryluk (ORCID: https://orcid.org/0000-0002-5047-6715)
- Miguel Vazquez (ORCID: https://orcid.org/0009-0002-8859-9494)
- Timothy A. Sutton (ORCID: https://orcid.org/0000-0002-4117-1434)
- Sushrut S. Waikar (ORCID: https://orcid.org/0000-0003-4004-326X)
- Ying‐Hua Cheng (ORCID: https://orcid.org/0000-0001-7871-8141)
- Michael T. Eadon (ORCID: https://orcid.org/0000-0003-3066-2876)
- Michael J. Ferkowicz (ORCID: https://orcid.org/0000-0002-9531-3899)
- Jonathan Himmelfarb (ORCID: https://orcid.org/0000-0002-3319-1224)
- Sanjay R. Jain (ORCID: https://orcid.org/0000-0003-2804-127X)
- Matthias Kretzler (ORCID: https://orcid.org/0000-0003-4064-0582)
- Pierre C. Dagher (ORCID: https://orcid.org/0000-0003-3321-5561)
- Daria Barwinska (ORCID: https://orcid.org/0000-0002-0776-3030)
- Jeffrey B. Hodgin (ORCID: https://orcid.org/0000-0003-0534-3048)
- Sylvia E. Rosas (ORCID: https://orcid.org/0000-0002-9903-4002)
- Tarek M. El‐Achkar (ORCID: https://orcid.org/0000-0003-4645-3614)
- Angela R. Sabo (ORCID: https://orcid.org/0000-0002-7496-8570)
- John F. O’Toole (ORCID: https://orcid.org/0000-0001-5929-1947)
Institutions
- Boston University (US)
- Joslin Diabetes Center (US)
- Cleveland Clinic (US)
- Harvard University (US)
- Johns Hopkins University (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- University of Michigan (US)
- Johns Hopkins Medicine (US)
- Indianapolis Zoo (US)
- University of Florida (US)
- Quantitative BioSciences (US)
- Richard L. Roudebush VA Medical Center (US)
- VA Pittsburgh Healthcare System (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- Columbia University (US)
- The University of Texas Southwestern Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-08-15
- DOI
- https://doi.org/10.1126/sciadv.adv8918
- Citations
- 6
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 4.84