Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma

Organs consist of parenchyma and stroma. Nishinakamura and colleagues induce renal stromal progenitors from mouse pluripotent stem cells (PSCs), and generate completely PSC-derived organoids that reproduce complex kidney structure. Organs consist of the parenchyma and stroma, the latter of which coordinates the generation of organotypic structures. Despite recent advances in organoid technology, induction of organ-specific stroma and recapitulation of complex organ configurations from pluripotent stem cells (PSCs) have remained challenging. By elucidating the in vivo molecular features of the renal stromal lineage at a single-cell resolution level, we herein establish an in vitro induction protocol for stromal progenitors (SPs) from mouse PSCs. When the induced SPs are assembled with two differentially induced parenchymal progenitors (nephron progenitors and ureteric buds), the completely PSC-derived organoids reproduce the complex kidney structure, with multiple types of stromal cells distributed along differentiating nephrons and branching ureteric buds. Thus, integration of PSC-derived lineage-specific stroma into parenchymal organoids will pave the way toward recapitulation of the organotypic architecture and functions.

Automated summary

Researchers have successfully induced renal stromal progenitors from mouse pluripotent stem cells (PSCs) and generated completely PSC-derived organoids that reproduce complex kidney structure. By understanding the molecular features of the renal stromal lineage, they established an in vitro induction protocol for stromal progenitors (SPs) from mouse PSCs. Assembling induced SPs with differentially induced parenchymal progenitors resulted in organoids that replicated the complex kidney structure.