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Войти в исследования Science advances · 2025
Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules.
СтатьяНазвание и аннотация: Перевод в очереди
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Asghari Mahla, Sabo Angela R, Barwinska Daria, Melo Ferreira Ricardo, Ferkowicz Michael J, Bowen William S, Cheng Ying-Hua, Gisch Debora L, Gulbronson Connor, Phillips Carrie L, Kelly Katherine J, Sutton Timothy A, Williams James C, Vazquez Miguel, O'Toole John, Palevsky Paul, Rosas Sylvia E, Waikar Sushrut S, Kiryluk Krzysztof, Parikh Chirag, Hodgin Jeffrey B, Sarder Pinaki, De Boer Ian H, Himmelfarb Jonathan, Kretzler Matthias, Kidney Precision Medicine Project, Jain Sanjay, Eadon Michael T, Winfree Seth, El-Achkar Tarek M, Dagher Pierre C
Аннотация
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.