Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury

ABSTRACT: Background: The inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Methods: Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI 72 hours post injury. Data was processed using the Seurat package. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation in in vitro human LECs. Results: We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved in endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models were also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. Conclusions: In this study, we uncover lymphatic vessel structural features of captured populations and injury-induced genetic changes. We further determine LEC gene expression is altered between injury models. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE236199 | GEO | 2024/02/20

REPOSITORIES: GEO