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

Summary: 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 embry...

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Main 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
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720303545
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author 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
author_facet 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
author_sort Hiraku Tsujimoto
collection DOAJ
description Summary: 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. : Tsujimoto et al. establish a differentiation system that separately generates multiple mesoderm lineages from hiPSCs. Three kidney progenitors, metanephric nephron progenitors (NPs), mesonephric NP-like cells, and the ureteric bud (UB), are further induced. They also generate interconnected kidney organoids from separately induced metanephric NPs and UB. Keywords: induced pluripotent stem cells, kidney, differentiation, mesonephros, metanephros, ureteric bud, collecting duct, nephrogenesis, single-cell analysis, organoid
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spelling doaj.art-1971024dbc1f452eb33770678d7f5ce12022-12-21T23:28:21ZengElsevierCell Reports2211-12472020-04-01311A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem CellsHiraku Tsujimoto0Tomoko Kasahara1Shin-ichi Sueta2Toshikazu Araoka3Satoko Sakamoto4Chihiro Okada5Shin-ichi Mae6Taiki Nakajima7Natsumi Okamoto8Daisuke Taura9Makoto Nasu10Tatsuya Shimizu11Makoto Ryosaka12Zhongwei Li13Masakatsu Sone14Makoto Ikeya15Akira Watanabe16Kenji Osafune17Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Mitsubishi Space Software, 5-4-36 Tsukaguchi-honmachi, Amagasaki, Hyogo 661-0001, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, 1333 San Pablo Street, MMR 618, Los Angeles, CA 90033, USADepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Corresponding authorSummary: 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. : Tsujimoto et al. establish a differentiation system that separately generates multiple mesoderm lineages from hiPSCs. Three kidney progenitors, metanephric nephron progenitors (NPs), mesonephric NP-like cells, and the ureteric bud (UB), are further induced. They also generate interconnected kidney organoids from separately induced metanephric NPs and UB. Keywords: induced pluripotent stem cells, kidney, differentiation, mesonephros, metanephros, ureteric bud, collecting duct, nephrogenesis, single-cell analysis, organoidhttp://www.sciencedirect.com/science/article/pii/S2211124720303545
spellingShingle 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
A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
Cell Reports
title A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
title_full A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
title_fullStr A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
title_full_unstemmed A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
title_short A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
title_sort modular differentiation system maps multiple human kidney lineages from pluripotent stem cells
url http://www.sciencedirect.com/science/article/pii/S2211124720303545
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