Dataset Information
Transcriptomic Analysis of Human Podocytes In Vitro: Effects of Differentiation and APOL1 Genotype.
Ontology highlight
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.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.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.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.
SUBMITTER: Yoshida T
PROVIDER: S-EPMC9831945 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Transcriptomic Analysis of Human Podocytes <i>In Vitro</i>: Effects of Differentiation and <i>APOL1</i> Genotype.
Kidney international reports 20221017 1
<h4>Introduction</h4>The mechanisms in podocytes that mediate the pathologic effects of the <i>APOL1</i> 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 <i>APOL1</i> HR variant-induced podocytopathy.<h4>Methods</h4>We conducted comprehensive transcriptomic analysis, including mRNA, microR ...[more]
