Renal Interstitial Cells Promote Nephron Regeneration by Secreting Prostaglandin E2

In organ regeneration, progrnitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation and differentiation. However, what kind of cells provide a native microenvironment for renal progenitor cells has not been clarified. Here, single-cell sequencing of zebrafish kidney revealed that fabp10 was a marker of renal interstitial cells (RICs), and the Tg(fabp10a:GFP) transgenic line can specifically label RICs in zebrafish kidney. The formation of RICs and nephrons are closely accompanied during nephron regeneration. RICs form a network to wrap the renal progenitor cell aggregates. RICs in close contact with cell aggregates express cyclooxygenase 2 and secrete prostaglandin 2 (PGE2). Inhibiting PGE2 production prevented nephrogenesis by reducing the proliferation and differentiation of progenitor cell aggregates. PGE2 promoted maturation of the nephron by activating the WNT signaling pathway in progenitor cell aggregates in cooperation with Wnt4a. These findings suggest that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.