Lgr5-positive endothelial progenitor cells occupy a tumor and injury prone niche in the kidney vasa recta

Mike R Wilson; Jeanne Holladay; Rachael Sheridan; Galen Hostetter; Bree Berghuis; Carrie Graveel; Curt Essenburg; Anderson Peck; Thai H Ho; Melissa Stanton; Ronald L Chandler

doi:10.1016/j.scr.2020.101849

Lgr5-positive endothelial progenitor cells occupy a tumor and injury prone niche in the kidney vasa recta

Stem Cell Res. 2020 Jul:46:101849. doi: 10.1016/j.scr.2020.101849. Epub 2020 May 20.

Authors

Affiliations

¹ Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
² Flow Cytometry Core, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
³ Pathology and Biorepository Core, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
⁴ Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
⁵ Small Animal Imaging Facility, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
⁶ Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, USA.
⁷ Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ 85259, USA.
⁸ Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA; Department of Women's Health, Spectrum Health System, Grand Rapids, MI 49341, USA. Electronic address: rlc@msu.edu.

PMID: 32464345
DOI: 10.1016/j.scr.2020.101849

Abstract

The Wnt pathway co-receptor, Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5), labels tumor-prone stem cell populations in certain types of tissue. In this study, we show that ARID1A and PIK3CA mutations in LGR5⁺ cells result in renal angiosarcomas in adult mice. The tumors originate in the renal medulla. We further show that LGR5 labels SOX17⁺/CD31⁺/CD34⁺/CD133⁺/AQP1⁺/CD146⁺ endothelial progenitor cells within the descending vasa recta or straight arterioles of the kidney, which are specialized capillaries that maintain medullary osmotic gradients necessary for water reabsorption and the production of concentrated urine. LGR5⁺ endothelial progenitor cells are tightly associated with contractile pericytes within the descending vasa recta. Long-term in vivo lineage tracing revealed that LGR5⁺ cells give rise to renal medullary vasculature. We further show that LGR5⁺ cells are activated in response to ischemic kidney injury. Our findings uncover a physiologically relevant endothelial progenitor cell population within the kidney vasa recta.

Keywords: Acute kidney injury; Ischemia; Stem cells; Vasa recta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Capillaries
Endothelial Progenitor Cells*
Kidney
Kidney Medulla
Mice
Neoplasms*
Receptors, G-Protein-Coupled / genetics

Substances

Lgr5 protein, mouse
Receptors, G-Protein-Coupled