Kidney Week

Abstract: SA-PO0023

Trajectory Analysis of Proximal Tubule Cells Reveals a VCAM1+, THY1+, PROM1+ Transitional State in the Kidneys

Session Information

• Intelligent Imaging and Omics: Phenotyping and Risk Stratification
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Artificial Intelligence, Digital Health, and Data Science

• 300 Artificial Intelligence, Digital Health, and Data Science

Authors

• Asghari, Mahla, Indiana University School of Medicine, Indianapolis, Indiana, United States

Mahla Asghari, MS

• Barwinska, Daria, Indiana University School of Medicine, Indianapolis, Indiana, United States

Daria Barwinska, PhD

• Sabo, Angela R., Indiana University School of Medicine, Indianapolis, Indiana, United States

Angela R. Sabo, PhD

• Ferkowicz, Michael J., Indiana University School of Medicine, Indianapolis, Indiana, United States

Michael J. Ferkowicz, PhD

• Bowen, William S., Indiana University School of Medicine, Indianapolis, Indiana, United States

William S. Bowen, PhD

• Cheng, Ying-Hua, Indiana University School of Medicine, Indianapolis, Indiana, United States

Ying-Hua Cheng, MD, PhD

• Melo Ferreira, Ricardo, Indiana University School of Medicine, Indianapolis, Indiana, United States

Ricardo Melo Ferreira, PhD

• Gisch, Debora L., Indiana University School of Medicine, Indianapolis, Indiana, United States

Debora L. Gisch, PhD

• Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States

Michael T. Eadon, MD, FASN

• Dagher, Pierre C., Indiana University School of Medicine, Indianapolis, Indiana, United States

Pierre C. Dagher, MD, FASN

• El-Achkar, Tarek M., Indiana University School of Medicine, Indianapolis, Indiana, United States

Tarek M. El-Achkar, MD, FASN

Background

Proximal tubule (PT) cells are fundamental to maintaining fluid, electrolyte, and nutrient balance in the kidney. Defining their health states and response to injury is crucial to understand the pathogenesis of kidney disease. THY1 is a stem cell marker that is highly expressed in PTs. PROM1 and VCAM1 are markers associated with kidney injury and repair. This study examines the dynamics of VCAM1, THY1 and PROM1 expression using spatial protein imaging.

Methods

CODEX imaging was conducted on 49 human kidney tissues with 41 markers from KPMP and HuBMAP. Samples were scaled, integrated, and clustered using an established pipeline. Clusters with high expression of THY1, PROM1, and VCAM1 were identified. Trajectory analysis for the VCAM1 enriched cluster was performed using Slingshot package.

Results

Our findings confirm the increase of PROM1 and a reduction of THY1 expression during chronic kidney disease. High expression of VCAM1 was observed in THY1+PROM1+ PT cells (figure1b-d). Trajectory analysis starting from VCAM1+ cluster reveals four paths: two towards healthy PTs (Trajectories 1 and 2), one towards PROM1+PT (Trajectory 3), and another towards THY1+PT (Trajectory 4)(figure1e). Trajectory 4 is the major lineage carrying the larger number of cells (figure 4j). Pseudotime protein expression analysis demonstrates consistent THY1 expression in Trajectory 4, transitioning from triple-positive PTs to THY1+PTs, while VCAM1 and PROM1 expression were reduced along this trajectory. Conversely, Trajectory 3 maintains high PROM1 expression leading to PROM1+PTs, with decreasing VCAM1 and THY1 expression.

Conclusion

VCAM1 is expressed during a transitional injury stage in PTs, co-expressed with THY1 and PROM1. Analyzing VCAM1 in association with these markers provides a better understanding of injury states.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025sgvrweb9