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 (mKPA) with expandable nephron progenitor cells (NPC) and ureteric bud (UB). Unexpectedly, versatile renal interstitial cells can be induced in kidney progenitor assembloid. 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. Cell populations profiling analysis of mouse kidney progenitor assembloids collected at Day 24 time point through 10x Genomics Multiome (scRNA/scATAC-seq) assays