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Multi-omic analysis of human kidney tissue identified medulla-specific gene expression patterns.

Kidney International 2023 November 22
The kidney medulla is a specialized region with important homeostatic functions. It has been implicated in genetic and developmental disorders along with ischemic and drug-induced injuries. Despite its role in kidney function and disease, the medulla's baseline gene expression and epigenomic signatures have not been well described in the adult human kidney. Here we generated and analyzed gene expression (RNA-seq), chromatin accessibility (ATAC-seq), chromatin conformation (Hi-C) and spatial transcriptomic data from the adult human kidney cortex and medulla. Tissue samples were obtained from macroscopically dissected cortex and medulla of tumor-adjacent normal material in nephrectomy specimens from five male patients. We used these carefully annotated specimens to reassign incorrectly labeled samples in the larger public Genotype-Tissue Expression (GTEx) Project, and to extract meaningful medullary gene expression signatures. Using integrated analysis of gene expression, chromatin accessibility and conformation profiles, we found insights into medulla development and function and then validated this by spatial transcriptomics and immunohistochemistry. Thus, our datasets provide a valuable resource for functional annotation of variants from genome-wide association studies and are freely accessible through an epigenome browser portal.

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