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Nephron organoids derived from human pluripotent stem cells model kidney development and injury

Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) would enable organ regeneration, disease modeling, and drug screening in vitro. We established an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form...

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Detalles Bibliográficos
Autores principales: Morizane, Ryuji, Lam, Albert Q., Freedman, Benjamin S., Kishi, Seiji, Valerius, M. Todd, Bonventre, Joseph V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747858/
https://www.ncbi.nlm.nih.gov/pubmed/26458176
http://dx.doi.org/10.1038/nbt.3392
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author Morizane, Ryuji
Lam, Albert Q.
Freedman, Benjamin S.
Kishi, Seiji
Valerius, M. Todd
Bonventre, Joseph V.
author_facet Morizane, Ryuji
Lam, Albert Q.
Freedman, Benjamin S.
Kishi, Seiji
Valerius, M. Todd
Bonventre, Joseph V.
author_sort Morizane, Ryuji
collection PubMed
description Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) would enable organ regeneration, disease modeling, and drug screening in vitro. We established an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-pattern into nephron structures. In both 2D and 3D culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle, and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity.
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spelling pubmed-47478582016-05-01 Nephron organoids derived from human pluripotent stem cells model kidney development and injury Morizane, Ryuji Lam, Albert Q. Freedman, Benjamin S. Kishi, Seiji Valerius, M. Todd Bonventre, Joseph V. Nat Biotechnol Article Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) would enable organ regeneration, disease modeling, and drug screening in vitro. We established an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-pattern into nephron structures. In both 2D and 3D culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle, and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity. 2015-11 /pmc/articles/PMC4747858/ /pubmed/26458176 http://dx.doi.org/10.1038/nbt.3392 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Morizane, Ryuji
Lam, Albert Q.
Freedman, Benjamin S.
Kishi, Seiji
Valerius, M. Todd
Bonventre, Joseph V.
Nephron organoids derived from human pluripotent stem cells model kidney development and injury
title Nephron organoids derived from human pluripotent stem cells model kidney development and injury
title_full Nephron organoids derived from human pluripotent stem cells model kidney development and injury
title_fullStr Nephron organoids derived from human pluripotent stem cells model kidney development and injury
title_full_unstemmed Nephron organoids derived from human pluripotent stem cells model kidney development and injury
title_short Nephron organoids derived from human pluripotent stem cells model kidney development and injury
title_sort nephron organoids derived from human pluripotent stem cells model kidney development and injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747858/
https://www.ncbi.nlm.nih.gov/pubmed/26458176
http://dx.doi.org/10.1038/nbt.3392
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