Abstract 011: Epigenetic Determinants Of Renin Cell Identity

Abstract

Renin secreting cells are restricted in adult mammals within the walls of renal arterioles near the entrance to the glomeruli and are therefore known as juxtaglomerular (JG) cells. These JG cells are critical for survival through the maintenance of homeostasis via the release of the peptide hormone renin in response to changes in blood pressure. By performing independently paired scATAC-seq and scRNA-seq during mouse kidney development, we sought to identify epigenetic markers of renin cell identity. While we lack spatial information, we identified putative JG cells through the identification of cells enriched in canonical markers (Ren1 and Akr1b7) of JG cell identity using both expression and accessibility derived measures of gene activity. We constructed a pseudotime trajectory of cells that lead to the mature JG population and performed pairwise comparisons of cell populations to identify the genomic regions and transcription factors (TFs) contributing to JG cell identity. As JG cells form along this trajectory, significantly different (Log2FC>0.5 and FDR<0.1) regions of accessible chromatin define the JG cell population. Within these open regions, the MEF2 family of TF motifs are significantly enriched (log10Padj > 20). We further identify a specific region of accessible chromatin (chr1:133345385-133345885) unique to the initial population of JG cells located within a Ren1 super enhancer previously identified by our group. This region is co-accessible with several regions of open chromatin within the greater Ren1 gene region (correlation > 0.75) where we identify putative binding sites for Mef2b, 2c, and 2d at these co-accessible regions. As the mature renin-expressing cells further differentiate into terminally differentiated cell populations including pericytes and mesangial cells, we continue to see significant enrichment of the MEF2 TF family within the JG cell population compared to downstream populations (log10Padj > 646.6891). Overall, we have presented the first investigation and finding using single-cell -omics of the JG cell population and uncover the importance of the MEF2 family of TFs as significant drivers of JG cell formation and identity.