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Kidney Week

Abstract: SA-PO350

Depot-Specific Alterations in Visceral Adipose Tissue-Derived Mesenchymal Stem Cells in CKD: Insights from Single-Cell RNA Sequencing

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Noh, Hyunjin, Soonchunhyang University Hospital, Yongsan-gu, Seoul, Korea (the Republic of)
  • Kim, Hyoungnae, Soonchunhyang University Hospital, Yongsan-gu, Seoul, Korea (the Republic of)
  • Yu, Mi ra, Soonchunhyang University Hospital, Yongsan-gu, Seoul, Korea (the Republic of)
  • Kwon, Soon hyo, Soonchunhyang University Hospital, Yongsan-gu, Seoul, Korea (the Republic of)
Background

Patients with chronic kidney disease (CKD) experience systemic conditions such as chronic inflammation, oxidative stress, and protein-energy wasting. While previous studies have explored inter-organ communication to understand these conditions, the specific changes occurring in adipose tissue within a uremic environment remain poorly understood. This study aimed to investigate the characteristics of visceral adipose tissue in CKD patients, with a focus on adipose tissue-derived mesenchymal stem cells (ADMSCs).

Methods

We collected retroperitoneal adipose tissue (RP) near the kidneys and omental adipose tissue (OM) from healthy kidney donors as well as CKD patients who underwent kidney transplantation or peritoneal catheter insertion. The characteristics of the stromal vascular fraction were evaluated using single-cell RNA sequencing. Additionally, adipose tissue fibrosis and the expression of thermogenic genes were assessed in the total adipose tissue from these two different depots.

Results

We harvested 66,668 cells. In the ADMSCs cluster of RP, CKD patients showed a significant upregulation of antioxidant genes, such as metallothioneins, SOD2, and GPX3. Gene Ontology and pathway analysis revealed that differentially expressed genes (DEGs) upregulated in CKD were related to ribosomal biogenesis and ferroptosis. We observed an increase in the S phase of the cell cycle in RP of CKD, accompanied by enhanced FOXO signaling pathway and cellular senescence to prevent DNA damage. In OM of CKD, DEGs specifically upregulated were related to ATP synthesis processes, including fatty acid β-oxidation, the TCA cycle, and oxidative phosphorylation in mitochondria. Additionally, the median cell size of adipocytes from CKD patients was significantly smaller than that of healthy controls, specifically in OM. Adipocytes of CKD OM showed a significant increase in the expression of thermogenic genes, such as UCP1, CIDEA, PGC1α, TBX1, and TMEM26.

Conclusion

We identified depot-specific alterations in ADMSCs and adipose tissue characteristics in CKD patients. Further investigations are needed to elucidate the potential role of these adipose tissue changes in the systemic conditions associated with CKD.

Funding

  • Government Support – Non-U.S.