Elimination of Reprogramming Transgenes Facilitates the Differentiation of Induced Pluripotent Stem Cells into Hepatocyte-like Cells and Hepatic Organoids
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jeong, Jaemin | - |
dc.contributor.author | Kim, Tae Hun | - |
dc.contributor.author | Kim, Myounghoi | - |
dc.contributor.author | Jung, Yun Kyung | - |
dc.contributor.author | Kim, Kyeong Sik | - |
dc.contributor.author | Shim, Sehwan | - |
dc.contributor.author | Jang, Hyosun | - |
dc.contributor.author | Jang, Won Il | - |
dc.contributor.author | Lee, Seung Bum | - |
dc.contributor.author | Choi, Dongho | - |
dc.date.accessioned | 2022-07-06T06:23:04Z | - |
dc.date.available | 2022-07-06T06:23:04Z | - |
dc.date.created | 2022-05-04 | - |
dc.date.issued | 2022-04 | - |
dc.identifier.issn | 2079-7737 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/138943 | - |
dc.description.abstract | Simple Summary The elimination of reprogramming transgenes affects the differentiation potential of human induced pluripotent stem cells (hiPSCs) at the early embryonic development stage, but not during the late stage of development into hepatocytes and hepatic organoids. Using an excisable polycistronic lentiviral system (STEMCCA, Cre-loxP system), we generated both transgene-carrying and transgene-free hiPSCs from human fibroblasts and demonstrated that the elimination of transgenes enhances the differentiation potential of iPSCs toward hepatocyte-like cells and the generation of hepatic organoids, exhibiting efficient hepatic differentiation. Our findings thus provide significant insights into the characteristics of iPSC-derived hepatic organoids. Hepatocytes and hepatic organoids (HOs) derived from human induced pluripotent stem cells (hiPSCs) are promising cell-based therapies for liver diseases. The removal of reprogramming transgenes can affect hiPSC differentiation potential into the three germ layers but not into hepatocytes and hepatic organoids in the late developmental stage. Herein, we generated hiPSCs from normal human fibroblasts using an excisable polycistronic lentiviral vector based on the Cre recombinase-mediated removal of the loxP-flanked reprogramming cassette. Comparing the properties of transgene-carrying and transgene-free hiPSCs with the same genetic background, the pluripotent states of all hiPSCs were quite similar, as indicated by the expression of pluripotent markers, embryonic body formation, and tri-lineage differentiation in vitro. However, after in vitro differentiation into hepatocytes, transgene-free hiPSCs were superior to the transgene-residual hiPSCs. Interestingly, the generation and hepatic differentiation of human hepatic organoids (hHOs) were significantly enhanced by transgene elimination from hiPSCs, as observed by the upregulated fetal liver (CK19, SOX9, and ITGA6) and functional hepatocyte (albumin, ASGR1, HNF4 alpha, CYP1A2, CYP3A4, and AAT) markers upon culture in differentiation media. Thus, the elimination of reprogramming transgenes facilitates hiPSC differentiation into hepatocyte-like cells and hepatic organoids with properties of liver progenitor cells. Our findings thus provide significant insights into the characteristics of iPSC-derived hepatic organoids. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.title | Elimination of Reprogramming Transgenes Facilitates the Differentiation of Induced Pluripotent Stem Cells into Hepatocyte-like Cells and Hepatic Organoids | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jung, Yun Kyung | - |
dc.contributor.affiliatedAuthor | Choi, Dongho | - |
dc.identifier.doi | 10.3390/biology11040493 | - |
dc.identifier.scopusid | 2-s2.0-85127653013 | - |
dc.identifier.wosid | 000785239900001 | - |
dc.identifier.bibliographicCitation | BIOLOGY-BASEL, v.11, no.4, pp.1 - 13 | - |
dc.relation.isPartOf | BIOLOGY-BASEL | - |
dc.citation.title | BIOLOGY-BASEL | - |
dc.citation.volume | 11 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 13 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.subject.keywordPlus | FIBROBLASTS | - |
dc.subject.keywordPlus | IMPROVES | - |
dc.subject.keywordPlus | MOUSE | - |
dc.subject.keywordAuthor | hiPSCs | - |
dc.subject.keywordAuthor | transgene-free | - |
dc.subject.keywordAuthor | Cre-loxP system | - |
dc.subject.keywordAuthor | hepatocyte differentiation | - |
dc.subject.keywordAuthor | hepatic organoids | - |
dc.identifier.url | https://www.mdpi.com/2079-7737/11/4/493 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.