Ureteric stromal progenitors give rise to kidney inner cortical pericytes via an arterial mural cell intermediate

Abstract

During kidney formation, segmented epithelial tubules and blood vessels develop within a heterogeneous and progressively patterned stroma. By E18.5, the murine renal stroma exhibits several transcriptionally and spatially distinct populations, including specialized stromal cells associated with the vasculature, termed mural cells. However, the precise contributions of stromal progenitor lineages to this stromal heterogeneity, as well as the dynamics of renal mural cell investment, remain unclear. Previous studies have described stromal progenitors in the developing cortex that transiently express the transcription factor Foxd1, as well as stromal progenitors in the ureter that express Tbx18, and have shown that both are capable of giving rise to renal stromal cells, including vascular mural cells. Here, we use pulse induction of Tbx18CreERT2 at different timepoints to elucidate the contribution of the Tbx18 population to stromal patterning. We show that the Tbx18-lineage, when induced at E12.5, gives rise to arterial mural cells, without ever progressing through a Foxd1+ cortical stromal progenitor state. These arterial mural cells are only transiently present along arteries during development, ultimately contributing instead to peritubular capillaries. When traced post-natally, the Tbx18-lineage gives rise to pericytes, which are enriched in S3-segment-associated, Cxcl14-enriched stroma in the inner cortex. We show that these pericytes arise directly from arterial mural cells seen earlier during development. These data help clarify a small portion of the complicated lineage relationships of renal stromal progenitors and their contribution to the kidney vascular-associated mural cells.

Keywords: Artery; Foxd1; Mural cell; Pericyte; Stroma; Tbx18.