A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells

• DOI: 10.1016/j.celrep.2020.03.040
• Publication Date: 2020-04-07T12:06:06Z
• Authors: Hiraku Tsujimoto; Tomoko Kasahara; Shin-ichi Sueta; Toshikazu Araoka; Satoko Sakamoto; Chihiro Okada; Shin-ichi Mae; Taiki Nakajima; Natsumi Okamoto; Daisuke Taura; Makoto Nasu; Tatsuya Shimizu; Makoto Ryosaka; Zhongwei Li; Masakatsu Sone; Makoto Ikeya; Akira Watanabe; Kenji Osafune
• Keywords: Pluripotent Stem Cells; 0301 basic medicine; kidney; induced pluripotent stem cells; QH301-705.5; organoid; Organogenesis; Cell Culture Techniques; nephrogenesis; Kidney; ureteric bud; collecting duct; Mesoderm; 03 medical and health sciences; single-cell analysis; Humans; Cell Lineage; Biology (General); Cells, Cultured; Cell Differentiation; Epithelial Cells; differentiation; Nephrons; Organoids; mesonephros; metanephros

Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage cells and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs, and ureteric bud (UB) cells, which constitute embryonic kidneys, in in vitro differentiation culture systems has not been fully investigated. Here, we create a culture system in which these mesoderm-like cell types and paraxial and lateral plate mesoderm-like cells are separately generated from hPSCs. We recapitulate nephrogenic niches from separately induced metanephric NP-like and UB-like cells, which are subsequently differentiated into glomeruli, renal tubules, and collecting ducts in vitro and further vascularized in vivo. Our selective differentiation protocols should contribute to understanding the mechanisms underlying human kidney development and disease and also supply cell sources for regenerative therapies.