Better Being Single? Omics Improves Kidney Organoids

Abstract

Context: Human kidney organoids are complex structures resembling nephron arrays, which can be derived in a variety of ways. Whether all of these differentiation protocols produce qualitatively similar organoid cell types is not yet clear. Subject of Review: A comparative analysis of 2 organoid differentiation protocols is recently reported in Cell Stem Cell [Wu et al.: Cell Stem Cell 2018;pii:S1934-5909(18)30491-0], using single cell RNA sequencing (scRNA-seq) as an analytical tool. This demonstrates that the 2 protocols have much in common, and that neither produces kidney cells in a pure or comprehensive manner. Ureteric lineages appear to be absent, and organoids are contaminated with non-kidney cell types, including neurons and muscle cells. Based on the scRNA-seq datasets, a new differentiation protocol is devised to reduce non-kidney cell types, without adversely affecting organoid epithelial cells. Second Opinion: Together with published analyses of a third differentiation protocol, these findings suggest more commonalities than differences between kidney organoid platforms, and identify critical strategies for functional improvement of these cellular structures.