title: Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells.
abstract: Recapitulating three-dimensional (3D) structures of complex organs, such as the kidney, from pluripotent stem cells (PSCs) is a major challenge. Here, we define the developmental origins of the metanephric mesenchyme (MM), which generates most kidney components. Unexpectedly, we find that posteriorly located T(+) MM precursors are developmentally distinct from Osr1(+) ureteric bud progenitors during the postgastrulation stage, and we identify phasic Wnt stimulation and stage-specific growth factor addition as molecular cues that promote their development into the MM. We then use this information to derive MM from PSCs. These progenitors reconstitute the 3D structures of the kidney in vitro, including glomeruli with podocytes and renal tubules with proximal and distal regions and clear lumina. Furthermore, the glomeruli are efficiently vascularized upon transplantation. Thus, by reevaluating the developmental origins of metanephric progenitors, we have provided key insights into kidney specification in vivo and taken important steps toward kidney organogenesis in vitro.
authors: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Atsuhiro
authors: A
authors: Taguchi
authors: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Yusuke
authors: Y
authors: Kaku
authors: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Tomoko
authors: T
authors: Ohmori
authors: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Sazia
authors: S
authors: Sharmin
authors: Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan; Japan Science and Technology Agency, CREST, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Minetaro
authors: M
authors: Ogawa
authors: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors: Hiroshi
authors: H
authors: Sasaki
authors: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan; Japan Science and Technology Agency, CREST, 2-2-1 Honjo, Kumamoto 860-0811, Japan. Electronic address: ryuichi@kumamoto-u.ac.jp.
authors: Ryuichi
authors: R
authors: Nishinakamura
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D009399:Nephrons / Q000166:cytology* / Q000378:metabolism; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers