Generation of renal tubular organoids from adult SOX9+ kidney progenitor cells

Abstract

The pathogenesis of several kidney diseases results in the eventual destruction of the renal tubular system, which can progress to end-stage renal disease. Previous studies have demonstrated the involvement of a population of SOX9-positive cells in kidney regeneration and repair process following kidney injury. However, the ability of these cells to autonomously generate kidney organoids has never been investigated. Here, we isolated SOX9+ kidney progenitor cells (KPCs) from both mice and humans, and tested their differentiation potential in vitro. The data showed that the human SOX9+ KPC could self-assembly into organoids with kidney-like morphology. We also used single-cell RNA sequencing to characterize the organoid cell populations, and identified four distinct types of renal tubular cells. Comparing to the induced pluripotent stem cell (iPSC)-derived kidney organoids, KPC demonstrated more tubular differentiation potential but failed to differentiate into glomerular cells. KPC-derived organoid formation involved expression of genes related to metanephric development and followed a similar mechanism to renal injury repair in acute kidney injury (AKI) patients. Altogether, our study provided a potentially useful approach to generate kidney tubular organoids for future application.