Figure 2.

Self-organization in renal organoids, and the importance of symmetry-breaking for large-scale anatomical realism. The top row shows the first-developed method for making renal organoids, in which iPS cells are differentiated into mixed renogenic stem cells (e.g. nephron precursors shown in blue, stromal precursors in green and ureteric bud precursors in pink). The cells organize themselves into individually realistic tubules but there is no realistic gross anatomy. The middle row begins with generation of separated stem cells groups (different protocols do this to different extents); generation of a ureteric bud (UB) epithelium, and then mixing it with the other cell types, breaks the symmetry of the system by including one unique, local source of ureteric bud. This develops into a single, connected tree, and nephrons organize around it appropriately. The bottom row shows a possible way of improving realism still by breaking the symmetry of the ureteric tree using local BMP application; this works in organoids made from ex-fetu renogenic stem cells but has not yet been done with iPS-derived ones.