Abstract: FR-PO1094
Single-Nucleus Transcriptome Revealed Differential Cell Fate of Human Proximal Tubular Cells with Aging
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Jung, Su Woong, Kyung Hee University, Seoul, Korea (the Republic of)
- Park, Jihoon, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Kim, Yang Gyun, Kyung Hee University, Seoul, Korea (the Republic of)
- Lee, Tae Hoon, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Korea (the Republic of)
- Moon, Ju young, Kyung Hee University, Seoul, Korea (the Republic of)
Background
Proximal tubular cell (PTC) is a high energy-requiring cell-type in the kidneys. But how this cell type ages remains incompletely understood throughout life course.
Methods
We explored transcriptional profiles through life time using the public dataset, Kidney Precision Medicine Project. We extracted the nuclei annotated as PTC from normal kidneys and discarded potential doublets that expressed other cell-type markers, which retained 18,765 nuclei.
Results
We found transcriptionally distinct 7 subclusters reannotated as healthy PT-1, healthy PT-2, stressed PT, scattered PT, injured PT-1, injured PT-2, and proliferating PT. Healthy PT-2 distinctively expressed PLIN2, a lipid dropet marker, and stressed PT showed enhanced expressions of ALDOB, PCK1, and GPX3. Scattered PT and injured PT-2 commonly expressed VIM, CD24, and S100A6, and injury PT population only expressed VCAM1. We found that healthy PT-2 showed the highest gene expression implicated in lipid metabolism, such as HMGCS2, ACSL1, and CPT1, and its PPAR-α signaling is upregulated than Healthy PT-1. In addition, scatter cells were enriched with lysosomal genes and has upregulation in glycolysis, oxidative phosphorylation, and actin cytoskeleon regulation compared to Healthy PT-1. In the trajectory analysis, healthy PT has two disintact pathes, one of which flow toward scattered PT through stressed PT and the other of which direct to injured PT. Each path had differential metabolic fate represented by enhanced and impaired fatty acid oxidation along the former and latter pathes.
Conclusion
PTC undergoes differential cell fate with aging on the view of gene expression and metabolism.