FoxD1 Cells to Mature Kidney Vasculature

Here we include a step-by-step breakdown of the analyses to reproduce the data presented in "Kidney vascular developmental trajectory reveals epigenetic determinants of renin cells".

Overview of the experimental design. (a) FoxD1+ derivative cells (incl. renin cells, VSMCs, MCs, pericytes (PCs), and fibroblasts (FBs)) are isolated from Foxd1Cre; mTmG mice. The FoxD1 promoter drives expression of Cre recombinase, excising the floxed tdTomato in the ROSA26 safe-harbor locus labelling all FoxD1 derivatives with green fluorescent protein. (b) Mouse kidney developmental time-points at E12, E18, P5, and P30 encompass the spectrum of nephrovascular development. Following kidney cell isolation, GFP-labeled cells are collected by FACS and both scRNA-seq and scATAC-seq were independently performed. Both data sets were integrated to track changes in the transcriptome and accessibilome during kidney vasculature maturation. AA: afferent arteriole

Overall, our goal was to leverage a mouse model (FoxD1Cre) that enriches for renin-expressing precursors and mature juxtaglomerular (JG) cells to establish a developmental trajectory and the corresponding genetic and epigenetic markers of mature JG cell populations. We did this by integrating scRNA-seq and scATAC-seq data from four developmental timepoints of mouse nephrogenesis. Overall, we establish support for the prominence of the MEF2 (myocyte enhancer factor-2) and NFI (nuclear factor I) families of transcription factors as significant drivers of JG cell maturation.