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Transcriptomic Analysis of Human Podocytes In Vitro : Effects of Differentiation and APOL1 Genotype.

Authors :
Yoshida T
Latt KZ
Rosenberg AZ
Shrivastav S
Heymann J
Halushka MK
Winkler CA
Kopp JB
Source :
Kidney international reports [Kidney Int Rep] 2022 Oct 17; Vol. 8 (1), pp. 164-178. Date of Electronic Publication: 2022 Oct 17 (Print Publication: 2023).
Publication Year :
2022

Abstract

Introduction: The mechanisms in podocytes that mediate the pathologic effects of the APOL1 high-risk (HR) variants remain incompletely understood, although various molecular and cellular mechanisms have been proposed. We previously established conditionally immortalized human urine-derived podocyte-like epithelial cell (HUPEC) lines to investigate APOL1 HR variant-induced podocytopathy.<br />Methods: We conducted comprehensive transcriptomic analysis, including mRNA, microRNA (miRNA), and transfer RNA fragments (tRFs), to characterize the transcriptional profiles in undifferentiated and differentiated HUPEC with APOL1 HR (G1/G2, 2 cell lines) and APOL1 low-risk (LR) (G0/G0, 2 cell lines) genotypes. We reanalyzed single-cell RNA-seq data from urinary podocytes from focal segmental glomerulosclerosis (FSGS) subjects to characterize the effect of APOL1 genotypes on podocyte transcriptomes.<br />Results: Differential expression analysis showed that the ribosomal pathway was one of the most enriched pathways, suggesting that altered function of the translation initiation machinery may contribute to APOL1 variant-induced podocyte injury. Expression of genes related to the elongation initiation factor 2 pathway was also enriched in the APOL1 HR urinary podocytes from single-cell RNA-seq, supporting a prior report on the role of this pathway in APOL1 -associated cell injury. Expression of microRNA and tRFs were analyzed, and the profile of small RNAs differed by both differentiation status and APOL1 genotype.<br />Conclusion: We have profiled the transcriptomic landscape of human podocytes, including mRNA, miRNA, and tRF, to characterize the effects of differentiation and of different APOL1 genotypes. The candidate pathways, miRNAs, and tRFs described here expand understanding of APOL1 -associated podocytopathies.

Details

Language :
English
ISSN :
2468-0249
Volume :
8
Issue :
1
Database :
MEDLINE
Journal :
Kidney international reports
Publication Type :
Academic Journal
Accession number :
36644347
Full Text :
https://doi.org/10.1016/j.ekir.2022.10.011