Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6

Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or o...

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Main Authors: Guye, Patrick, Kipniss, Nathan, Velazquez, Jeremy J., Schoenfeld, Eldi, Kiani, Samira, Griffith, Linda G., Weiss, Ron, Ebrahimkhani, Mohammad Reza
Other Authors: MIT Synthetic Biology Center
Format: Article
Language:en_US
Published: Nature Publishing Group 2016
Online Access:http://hdl.handle.net/1721.1/101729
https://orcid.org/0000-0003-0396-2443
https://orcid.org/0000-0003-1736-0937
https://orcid.org/0000-0002-1801-5548
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author Guye, Patrick
Kipniss, Nathan
Velazquez, Jeremy J.
Schoenfeld, Eldi
Kiani, Samira
Griffith, Linda G.
Weiss, Ron
Ebrahimkhani, Mohammad Reza
author2 MIT Synthetic Biology Center
author_facet MIT Synthetic Biology Center
Guye, Patrick
Kipniss, Nathan
Velazquez, Jeremy J.
Schoenfeld, Eldi
Kiani, Samira
Griffith, Linda G.
Weiss, Ron
Ebrahimkhani, Mohammad Reza
author_sort Guye, Patrick
collection MIT
description Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues.
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spelling mit-1721.1/1017292022-10-01T07:59:39Z Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6 Guye, Patrick Kipniss, Nathan Velazquez, Jeremy J. Schoenfeld, Eldi Kiani, Samira Griffith, Linda G. Weiss, Ron Ebrahimkhani, Mohammad Reza MIT Synthetic Biology Center Massachusetts Institute of Technology. Department of Biological Engineering MIT Emergent Behaviors of Integrated Cellular Systems Center Guye, Patrick Ebrahimkhani, Mohammad Reza Kipniss, Nathan Velazquez, Jeremy J. Schoenfeld, Eldi Kiani, Samira Griffith, Linda G. Weiss, Ron Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues. National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (NSF CBET-0939511) Synthetic Biology Engineering Research Center National Institutes of Health (U.S.) (P50GM098792) Ernst Schering Foundation Swiss National Science Foundation 2016-03-17T00:31:34Z 2016-03-17T00:31:34Z 2016-01 2015-06 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/101729 Guye, Patrick, Mohammad R. Ebrahimkhani, Nathan Kipniss, Jeremy J. Velazquez, Eldi Schoenfeld, Samira Kiani, Linda G. Griffith, and Ron Weiss. “Genetically Engineering Self-Organization of Human Pluripotent Stem Cells into a Liver Bud-Like Tissue Using Gata6.” Nat Comms 7 (January 6, 2016): 10243. https://orcid.org/0000-0003-0396-2443 https://orcid.org/0000-0003-1736-0937 https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1038/ncomms10243 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Publishing Group
spellingShingle Guye, Patrick
Kipniss, Nathan
Velazquez, Jeremy J.
Schoenfeld, Eldi
Kiani, Samira
Griffith, Linda G.
Weiss, Ron
Ebrahimkhani, Mohammad Reza
Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
title Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
title_full Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
title_fullStr Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
title_full_unstemmed Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
title_short Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
title_sort genetically engineering self organization of human pluripotent stem cells into a liver bud like tissue using gata6
url http://hdl.handle.net/1721.1/101729
https://orcid.org/0000-0003-0396-2443
https://orcid.org/0000-0003-1736-0937
https://orcid.org/0000-0002-1801-5548
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