Transcriptomes of Major Proximal Tubule Cell Culture Models

Area of Science:

• Nephrology
• Molecular Biology
• Cell Biology

Background:

• Cultured renal proximal tubule cell lines are crucial for studying kidney physiology, pathophysiology, toxicology, and pharmacology.
• The suitability of cell lines depends on their gene expression profiles, which can be analyzed using RNA sequencing (RNA-Seq).

Purpose of the Study:

• To catalog expressed genes in different proximal tubule cell lines using RNA-Seq.
• To compare the transcriptomic profiles of various cell lines with native proximal tubule cells.
• To identify cell lines optimal for modeling specific renal proximal tubule functions.

Main Methods:

• Cultured fourteen proximal tubule cell lines from six species on permeable supports.
• Performed RNA sequencing (RNA-Seq) to profile gene expression.
• Mapped cell line transcriptomes to gene sets representing proximal tubule functions.

Main Results:

• Cell line transcriptomes showed variable matches to native proximal tubule transcripts; Opossum kidney (OK) cells had the highest match (45%).
• Significant variability in proximal tubule marker expression was observed even between different sources of the same cell line (e.g., OK cells).
• Different cell lines were found to be optimal for modeling distinct proximal tubule functions, such as transport and metabolism.

Conclusions:

• No single cell line fully replicates the transcriptome of native proximal tubule cells.
• Certain tested cell lines are valuable for investigating specific metabolic and transport processes characteristic of the renal proximal tubule.