Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells
Intestinal organoids derived from human pluripotent stem cells (hPSCs) are valuable in vitro research models that enable simplified access to human gastrointestinal tissues. Here, we report the in vitro generation of enterospheres (hEnS) from hPSC-derived gastrointestinal epithelial precursors. hEnS...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221367111730334X |
| _version_ | 1811312231921483776 |
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| author | Rohan R. Nadkarni Soumeya Abed Brian J. Cox Sonam Bhatia Jennifer T. Lau Michael G. Surette Jonathan S. Draper |
| author_facet | Rohan R. Nadkarni Soumeya Abed Brian J. Cox Sonam Bhatia Jennifer T. Lau Michael G. Surette Jonathan S. Draper |
| author_sort | Rohan R. Nadkarni |
| collection | DOAJ |
| description | Intestinal organoids derived from human pluripotent stem cells (hPSCs) are valuable in vitro research models that enable simplified access to human gastrointestinal tissues. Here, we report the in vitro generation of enterospheres (hEnS) from hPSC-derived gastrointestinal epithelial precursors. hEnS are cystic spheroids with a simple uniform structure composed entirely of intestinal epithelium. hEnS express markers of mature brush border cells and share a transcriptome profile similar to that of more mature intestinal organoids. Modulation of signaling cues enables control of hEnS growth and differentiation, including long-term propagation. We show that hEnS can be exploited for functional studies: hEnS display an innate immune response when treated with enteric pathogens, and transgenic modification of hEnS with a fluorescence cell-cycle reporter enables hEnS-forming stem cell enrichment. Our work establishes hEnS as an accessible and tractable in vitro modeling system for studying human gastrointestinal biology. |
| first_indexed | 2024-04-13T10:32:38Z |
| format | Article |
| id | doaj.art-41d69864262a46b59e95fb751b24aedd |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-13T10:32:38Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-41d69864262a46b59e95fb751b24aedd2022-12-22T02:50:08ZengElsevierStem Cell Reports2213-67112017-09-019389791210.1016/j.stemcr.2017.07.024Functional Enterospheres Derived In Vitro from Human Pluripotent Stem CellsRohan R. Nadkarni0Soumeya Abed1Brian J. Cox2Sonam Bhatia3Jennifer T. Lau4Michael G. Surette5Jonathan S. Draper6McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, CanadaMcMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Physiology, University of Toronto, Toronto ON, CanadaMcMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, CanadaMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8N 3Z5, CanadaMcMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, CanadaIntestinal organoids derived from human pluripotent stem cells (hPSCs) are valuable in vitro research models that enable simplified access to human gastrointestinal tissues. Here, we report the in vitro generation of enterospheres (hEnS) from hPSC-derived gastrointestinal epithelial precursors. hEnS are cystic spheroids with a simple uniform structure composed entirely of intestinal epithelium. hEnS express markers of mature brush border cells and share a transcriptome profile similar to that of more mature intestinal organoids. Modulation of signaling cues enables control of hEnS growth and differentiation, including long-term propagation. We show that hEnS can be exploited for functional studies: hEnS display an innate immune response when treated with enteric pathogens, and transgenic modification of hEnS with a fluorescence cell-cycle reporter enables hEnS-forming stem cell enrichment. Our work establishes hEnS as an accessible and tractable in vitro modeling system for studying human gastrointestinal biology.http://www.sciencedirect.com/science/article/pii/S221367111730334Xenterospheresintestinal organoidsintestinehuman pluripotent stem cellsin vitro differentiationWnt signalinginnate immunity |
| spellingShingle | Rohan R. Nadkarni Soumeya Abed Brian J. Cox Sonam Bhatia Jennifer T. Lau Michael G. Surette Jonathan S. Draper Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells Stem Cell Reports enterospheres intestinal organoids intestine human pluripotent stem cells in vitro differentiation Wnt signaling innate immunity |
| title | Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells |
| title_full | Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells |
| title_fullStr | Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells |
| title_full_unstemmed | Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells |
| title_short | Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells |
| title_sort | functional enterospheres derived in vitro from human pluripotent stem cells |
| topic | enterospheres intestinal organoids intestine human pluripotent stem cells in vitro differentiation Wnt signaling innate immunity |
| url | http://www.sciencedirect.com/science/article/pii/S221367111730334X |
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