In vitro generation of a ureteral organoid from pluripotent stem cells

The ureter is the outlet for urine produced by the kidney. Recent advances in stem cell biology have enabled the in vitro generation of kidney organoids from pluripotent stem cells (PSCs), but they lack the ureter, which hinders the smooth drainage of urine. By mimicking the in vivo developmental process of ureteral stromal progenitors (SPs) from the posterior intermediate mesoderm, we report here in vitro induction protocols for ureteral SPs from mouse and human PSCs. When the induced SPs were combined with ureteral epithelia derived from mouse embryos, the elongated, multilayered ureteral structure was reconstituted, exhibiting peristaltic constriction. The ureter-like spherical organoids entirely derived from mouse PSCs can also be generated by combining the induced SPs and the epithelial progenitor, the ureteric bud. Furthermore, ureteral SPs induced from TBX18-deficient human PSCs recapitulate the disease state of a congenital anomaly of the urinary tract. Therefore, our induction protocols for ureteral SPs will be useful for the elucidation of ureteral development and disease, and will be an important step towards functional kidney organoids with urine flow. Overall design: Kidney mRNA profiles of embryonic day E11.5, E13.5, E15.5, E17.5, postnatal day 0 and day7 at single cell resolution. mRNA profiles of Induced stromal progenitors from mouse ESCs and cultured ureters at single cell resolution