Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids
Summary: Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118300328 |
| _version_ | 1819146899606732800 |
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| author | Ran-Ran Zhang Masaru Koido Tomomi Tadokoro Rie Ouchi Tatsuya Matsuno Yasuharu Ueno Keisuke Sekine Takanori Takebe Hideki Taniguchi |
| author_facet | Ran-Ran Zhang Masaru Koido Tomomi Tadokoro Rie Ouchi Tatsuya Matsuno Yasuharu Ueno Keisuke Sekine Takanori Takebe Hideki Taniguchi |
| author_sort | Ran-Ran Zhang |
| collection | DOAJ |
| description | Summary: Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm. We found that combinatorial EGF, VEGF, FGF2, Chir99021, and A83-01 treatments selectively amplify storable PGECs up to 1021 cell scale without any gene transduction or feeder use. PGECs, compared with induced pluripotent stem cells, showed stable differentiation propensity into multiple endodermal lineages without teratoma formation. Furthermore, transplantation of PGEC-derived liver bud organoids showed therapeutic potential against fulminant liver failure. Together, the robustly amplified PGECs may be a promising cellular source for endoderm-derived organoids in studying human development, modeling disease, and, ultimately, therapy. : In this article, Takebe, Taniguchi, and colleagues derived a unique population of CDX2+ posterior endoderm progenitors (PGECs) from human pluripotent stem cells that are highly expandable and storable in a chemically defined condition. CDX2+ endoderm progenitors can form multiple endodermal organoids. Transplantation of human liver bud organoids from robustly propagated PGECs rescued lethal liver failure of immunodeficient mice. Keywords: progenitors, posterior gut endoderm cells, organoid, liver bud, transplant, human, pluripotent stem cells, iPSC, CDX2, intestine |
| first_indexed | 2024-12-22T13:21:15Z |
| format | Article |
| id | doaj.art-3431a582b18a40fc825fb236fb5689da |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-22T13:21:15Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-3431a582b18a40fc825fb236fb5689da2022-12-21T18:24:27ZengElsevierStem Cell Reports2213-67112018-03-01103780793Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver OrganoidsRan-Ran Zhang0Masaru Koido1Tomomi Tadokoro2Rie Ouchi3Tatsuya Matsuno4Yasuharu Ueno5Keisuke Sekine6Takanori Takebe7Hideki Taniguchi8Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Division of Gastroenterology, Hepatology & Nutrition, Developmental Biology, Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USADepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, JapanDepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, JapanDivision of Gastroenterology, Hepatology & Nutrition, Developmental Biology, Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USADepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, JapanDepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, JapanDepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, JapanDepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Division of Gastroenterology, Hepatology & Nutrition, Developmental Biology, Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Advanced Medical Research Center, Yokohama City University, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Corresponding authorDepartment of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa 236-0004, Japan; Division of Gastroenterology, Hepatology & Nutrition, Developmental Biology, Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA; Corresponding authorSummary: Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm. We found that combinatorial EGF, VEGF, FGF2, Chir99021, and A83-01 treatments selectively amplify storable PGECs up to 1021 cell scale without any gene transduction or feeder use. PGECs, compared with induced pluripotent stem cells, showed stable differentiation propensity into multiple endodermal lineages without teratoma formation. Furthermore, transplantation of PGEC-derived liver bud organoids showed therapeutic potential against fulminant liver failure. Together, the robustly amplified PGECs may be a promising cellular source for endoderm-derived organoids in studying human development, modeling disease, and, ultimately, therapy. : In this article, Takebe, Taniguchi, and colleagues derived a unique population of CDX2+ posterior endoderm progenitors (PGECs) from human pluripotent stem cells that are highly expandable and storable in a chemically defined condition. CDX2+ endoderm progenitors can form multiple endodermal organoids. Transplantation of human liver bud organoids from robustly propagated PGECs rescued lethal liver failure of immunodeficient mice. Keywords: progenitors, posterior gut endoderm cells, organoid, liver bud, transplant, human, pluripotent stem cells, iPSC, CDX2, intestinehttp://www.sciencedirect.com/science/article/pii/S2213671118300328 |
| spellingShingle | Ran-Ran Zhang Masaru Koido Tomomi Tadokoro Rie Ouchi Tatsuya Matsuno Yasuharu Ueno Keisuke Sekine Takanori Takebe Hideki Taniguchi Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids Stem Cell Reports |
| title | Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids |
| title_full | Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids |
| title_fullStr | Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids |
| title_full_unstemmed | Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids |
| title_short | Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids |
| title_sort | human ipsc derived posterior gut progenitors are expandable and capable of forming gut and liver organoids |
| url | http://www.sciencedirect.com/science/article/pii/S2213671118300328 |
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