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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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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. |
format | Online Article Text |
id | pubmed-4747858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
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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