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Abstract: FR-PO373

Multi-Omic Analyses of Primary Kidney Tissue Identifies Medulla-Specific Genes and Transcriptional Regulators

Session Information

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Haug, Stefan, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
  • Li, Yong, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
  • Muthusamy, Selvaraj, Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, United States
  • Kottgen, Anna, Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany
  • Akilesh, Shreeram, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, United States

The kidney medulla is a key regulator of salt and water balance. Despite this vital function, it is relatively understudied, including its contribution to inherited or acquired kidney disease. To fill this gap, we generated and analyzed gene expression (RNA-seq), chromatin accessibility (ATAC-seq) and chromatin conformation (HiC) data derived from human cortex and medulla tissue in order to identify patterns of medulla-specific gene expression and regulation.


Macrodissected matched pairs of healthy cortex and medulla tissue were sampled from kidneys of four adult tumor nephrectomy patients. RNA-seq, ATAC-seq and HiC data were generated and analyzed to identify differentially expressed genes, differentially accessible regions and differential loops between cortex and medulla. We also analyzed our data together with publicly available single nucleus RNA-seq data and the GTEx database to calibrate and extend our findings.


Over 2,300 genes were differentially expressed (padj <0.01, log2-fold change >1) between cortex and medulla. Our carefully annotated samples and gene expression analysis helped to re-assign mislabeled samples in the GTEx database. Medulla-specific genes expressed in the adult were overrepresented among kidney development pathways and included many genes relevant for kidney disease like UMOD, SLC12A1 and EGF.
By incorporating genome-wide maps of chromatin accessibility and conformation, we defined the regulatory landscape around exemplar medullary genes (SLCO3A1, CLDN14 and WNT7B). Next, we examined transcription factor (TF) motifs in accessible chromatin regions and predicted an important role for POU3F3 in the medulla, which we confirmed by immunohistochemistry. POU3F3 has been previously shown to be important in mouse kidney development, but here we show that it is also expressed in the adult human medulla, where it may direct expression of ~17% of medulla-specific genes.


The reference-quality functional genomic datasets generated in this study elucidate the regulatory differences between human kidney cortex and medulla. This valuable resource will help us better understand diseases and conditions originating in the medullary portion of the human kidney.


  • Government Support – Non-U.S.