GSE117211
Kidney micro-organoids generated in suspension culture
Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scale-up production of kidney cell types in vitro. We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Each micro-organoid contains 6-10 nephrons surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. Ligand-receptor mapping identified TGFß signalling between stromal and epithelial cell types as likely to result in fibrotic changes observed with long-term culture. The addition of an ALK4 inhibitor suppressed stromal expansion, maintaining epithelial morphology and improving maturation. This suspension culture micro-organoid methodology resulted in a 3-4-fold increase in final cell yield compared to static culture, thereby representing an economical approach to the production of kidney cells for various biological applications. Overall design: Single cell RNA-seq from a pool of kidney micro-organoids.