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논문분류	춘계학술대회 초록집
제목	RNA-seq profiling of microdissected glomeruli in IgA nephropathy patients
저자	Jae Wook Lee2, Sehoon Park1, Seung Hee Yang4, Kyung Chul Moon3, Dong Ki Kim1, Yon Su Kim1, Hajeong Lee1
출판정보	2018; 2018(1):
키워드	immunoglobulin A nephropathy \| genomics \| rna sequencing
초록	Objectives: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and also a leading cause of chronic kidney disease and renal failure. To identify early gene-expression changes in IgAN, we profiled the transcriptome in microdissected human glomeruli using deep sequencing of RNA species (RNA-seq). Methods: Glomeruli were microdissected from the biopsy specimen obtained from 14 IgAN patients with preserved renal function (eGFR > 60 mL/min/1.73m2 and proteinuria < 3 g/d). As negative controls, normal glomeruli were obtained from patients undergoing nephrectomy (n=10). Glomerular mRNAs were captured using oligo-dT primers and made into cDNA libraries for Illumina sequencing. After mapping to the human reference genome (GRCh38 primary assembly), reads uniquely mapping to Ensembl genes were summarized as integer counts. Wald test for a negative binomial model was used to call differentially expressed genes. Results: Each library produced 25-70 million pairs of reads, more than 70% of which were uniquely aligned to the human genome. Of 16,435 Ensembl genes with >20 reads in more than half samples, 1394 were upregulated and 1144 downregulated in the IgAN glomeruli with adjusted p-value < 0.01. Upregulated genes included signaling molecules (BTK, LYN, SYK, PI3K, TGFβ, TNF, TNFRSF1A/B, NFKB1, PLCG2, STAT3), actin-related molecules (ACTR3, ARPC1B, CAPZA1), and regulators of apoptosis (MCL1, BCL2A, BCL2L11, BCL2L13). Among low expressed genes were proto-oncogenes (JUN, FOS) and RNA- processing factors (PRPF31, PRPF3). Gene-set enrichment analysis revealed biological pathways significantly enriched in the IgAN transcriptome, namely chemokine signaling, B cell receptor or Fcɤ receptor signaling, actin cytoskeleton regulation, cell proliferation, and protein/RNA processing. Conclusions: RNA-seq profiling of microdissected glomeruli identified a number of differentially expressed genes and significantly enriched pathways potentially useful for monitoring and treatment of IgA nephropathy. Further studies are needed to define the biological significance of these findings. fig 1. PCA plot
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