Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells
Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the i...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96280 https://orcid.org/0000-0003-1736-0937 |
| _version_ | 1826195075509518336 |
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| author | Forster, Ryan Chiba, Kunitoshi Schaeffer, Lorian Regalado, Samuel G. Lai, Christine S. Gao, Qing Kiani, Samira Farin, Henner F. Clevers, Hans Cost, Gregory J. Chan, Andy Rebar, Edward J. Urnov, Fyodor D. Gregory, Philip D. Jaenisch, Rudolf Hockemeyer, Dirk Pachter, Lior, 1973- |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Forster, Ryan Chiba, Kunitoshi Schaeffer, Lorian Regalado, Samuel G. Lai, Christine S. Gao, Qing Kiani, Samira Farin, Henner F. Clevers, Hans Cost, Gregory J. Chan, Andy Rebar, Edward J. Urnov, Fyodor D. Gregory, Philip D. Jaenisch, Rudolf Hockemeyer, Dirk Pachter, Lior, 1973- |
| author_sort | Forster, Ryan |
| collection | MIT |
| description | Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs. |
| first_indexed | 2024-09-23T10:06:32Z |
| format | Article |
| id | mit-1721.1/96280 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:06:32Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/962802022-09-26T15:45:16Z Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells Forster, Ryan Chiba, Kunitoshi Schaeffer, Lorian Regalado, Samuel G. Lai, Christine S. Gao, Qing Kiani, Samira Farin, Henner F. Clevers, Hans Cost, Gregory J. Chan, Andy Rebar, Edward J. Urnov, Fyodor D. Gregory, Philip D. Jaenisch, Rudolf Hockemeyer, Dirk Pachter, Lior, 1973- Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Jaenisch, Rudolf Kiani, Samira Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs. National Institutes of Health (U.S.) (Grant R37-CA084198) National Institutes of Health (U.S.). (Grant RO1-CA087869) National Institutes of Health (U.S.) (Grant RO1-HD045022) Howard Hughes Medical Institute (Grant) 2015-03-31T16:25:47Z 2015-03-31T16:25:47Z 2014-06 2014-05 Article http://purl.org/eprint/type/JournalArticle 22136711 http://hdl.handle.net/1721.1/96280 Forster, Ryan, Kunitoshi Chiba, Lorian Schaeffer, Samuel G. Regalado, Christine S. Lai, Qing Gao, Samira Kiani, et al. “Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells.” Stem Cell Reports 2, no. 6 (June 2014): 838–852. https://orcid.org/0000-0003-1736-0937 en_US http://dx.doi.org/10.1016/j.stemcr.2014.05.001 Stem Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Forster, Ryan Chiba, Kunitoshi Schaeffer, Lorian Regalado, Samuel G. Lai, Christine S. Gao, Qing Kiani, Samira Farin, Henner F. Clevers, Hans Cost, Gregory J. Chan, Andy Rebar, Edward J. Urnov, Fyodor D. Gregory, Philip D. Jaenisch, Rudolf Hockemeyer, Dirk Pachter, Lior, 1973- Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells |
| title | Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells |
| title_full | Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells |
| title_fullStr | Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells |
| title_full_unstemmed | Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells |
| title_short | Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells |
| title_sort | human intestinal tissue with adult stem cell properties derived from pluripotent stem cells |
| url | http://hdl.handle.net/1721.1/96280 https://orcid.org/0000-0003-1736-0937 |
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