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Updated: Jun 13, 2025
A Quantitative Detection Method for MicroRNAs in the Kidney of an Ischemic Kidney Injury Mouse Model
Published on: September 11, 2020
Spatiotemporal transcriptomic analysis during cold ischemic injury to the murine kidney reveals compartment-specific
Srujan Singh1,2, Shishir Kumar Patel3, Ryo Matsuura3
1Center for Computational Biology, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Abstract:
Kidney transplantation is the gold standard treatment strategy for end-stage renal disease. Deceased donor kidneys usually undergo cold storage until kidney transplantation, leading to cold ischemia injury that may contribute to poor graft outcomes. However, the molecular characterization of potential mechanisms of cold ischemia injury remains incomplete. To bridge this knowledge gap, we leveraged spatial transcriptomics technology to perform full transcriptome characterization of cold ischemia injury (0-48 hours) using a murine model. We developed a computational workflow to identify spatiotemporal transcriptomic changes that accompany the injury pathophysiology in a compartment-specific manner. We identified potential metabolic reprogramming preferentially within the kidney inner medulla displaying strong oxidative phosphorylation signature in an ischemic environment. We found commonalities between the spatiotemporal transcriptomic presentation of cold ischemia and warm ischemia‒reperfusion injury, including an induction of an anti-viral like immune response throughout the renal tissue. Altogether, these systems-level biological insights enabled by our full transcriptome temporal characterization unveil a molecular basis for how cold ischemia injury may negatively affect kidney outcomes. Moreover, our spatial analyses highlight pathological developments deep within the renal tissue, suggesting potential opportunities for new insights beyond biopsy-focused superficial tissue examinations. We also developed an interactive online browser at https://jef.works/vitessce-cold-ischemia/ to facilitate exploration of our results by the broader scientific and clinical community.
Insights
Cold storage of donor kidneys causes cold ischemia injury, impacting transplant success. Spatial transcriptomics reveals molecular changes, including metabolic shifts and immune responses, offering new insights into kidney injury mechanisms.
Area of Science:
- Nephrology
- Molecular Biology
- Bioinformatics
Background:
- Kidney transplantation is a primary treatment for end-stage renal disease.
- Cold storage of deceased donor kidneys can lead to cold ischemia injury (CII), negatively affecting graft outcomes.
- The molecular mechanisms underlying CII are not fully understood.
Purpose of the Study:
- To comprehensively characterize the molecular mechanisms of cold ischemia injury (CII) in kidney grafts.
- To investigate the spatiotemporal transcriptomic changes during CII using spatial transcriptomics.
- To identify specific kidney compartments affected by CII.
Main Methods:
- Utilized a murine model to study kidney tissues subjected to cold ischemia for 0-48 hours.
- Applied spatial transcriptomics for full transcriptome characterization.
- Developed a computational workflow to analyze spatiotemporal transcriptomic data in a compartment-specific manner.
Main Results:
- Identified significant metabolic reprogramming in the kidney inner medulla, characterized by increased oxidative phosphorylation under ischemic conditions.
- Observed an induction of an anti-viral-like immune response across renal tissues, similar to warm ischemia-reperfusion injury.
- Spatial analysis revealed pathological changes deep within the kidney tissue.
Conclusions:
- The study provides systems-level insights into the molecular basis of cold ischemia injury in kidney transplantation.
- Findings highlight the importance of spatial analysis for understanding kidney injury beyond superficial tissue examination.
- An interactive online browser was created to share these valuable transcriptomic data with the research community.
