Spatially-patterned and functional kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling

The paired kidneys are the central organs of homeostasis for our body systems, the sophisticated structure and complex cells composition underpins kidneys’ functions. Here we report the generation of mouse kidney progenitor assembloid (KPA) with expandable nephron progenitor cells (NPC) and ureteric bud (UB). Unexpectedly, versatile renal interstitial cells can be induced in kidney progenitor assembloids. Mechanistically, some NPC can be transdifferentiated into interstitial progenitor cells (IPCs) in KPA context, then induced IPCs differentiate into various renal interstitial cells. These kidney progenitors-based KPA highly resembled postnatal mouse kidneys with well pattern and showed essential renal physiological functions. E12.5 mouse kidneys and expandable kidney progenitors-derived mouse kidney progenitor assembloids (KPA) were cultured under optimized stage-based media-v2, and collected at different time point. RNA samples were extracted and then subjected to bulk RNA-Seq analysis.