title: Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation.
abstract: Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator-like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm-like structures. Microarray analysis of sorted iPS cell-derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell-derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell-derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases.
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, and.
authors.forename: Sazia
authors.initials: S
authors.lastname: Sharmin
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, and.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, and.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kaku
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, and Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan;
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshimura
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohmori
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan;
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Sakuma
authors.affiliation: Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan;
authors.forename: Masashi
authors.initials: M
authors.lastname: Mukoyama
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and.
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, and Japan Science and Technology Agency, CREST, Kumamoto, Japan ryuichi@kumamoto-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007678:Kidney Glomerulus / Q000098:blood supply*; D051379:Mice; D050199:Podocytes / Q000502:physiology* / Q000648:ultrastructure
keywords: kidney development; podocyte; stem cell