Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins
Fallopian tube epithelial cells (FTECs) play a significant role in the development of high-grade serous ovarian cancer (HGSOC), but their utilization in in vitro experiments presents challenges. To address these limitations, induced pluripotent stem cells (iPSCs) have been employed as a potential so...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/22/2635 |
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| author | Yu-Hsun Chang Kun-Chi Wu Kai-Hung Wang Dah-Ching Ding |
| author_facet | Yu-Hsun Chang Kun-Chi Wu Kai-Hung Wang Dah-Ching Ding |
| author_sort | Yu-Hsun Chang |
| collection | DOAJ |
| description | Fallopian tube epithelial cells (FTECs) play a significant role in the development of high-grade serous ovarian cancer (HGSOC), but their utilization in in vitro experiments presents challenges. To address these limitations, induced pluripotent stem cells (iPSCs) have been employed as a potential solution, driven by the hypothesis that orthologous iPSCs may offer superior differentiation capabilities compared with their non-orthologous counterparts. Our objective was to generate iPSCs from FTECs, referred to as FTEC-iPSCs, and compare their differentiation potential with iPSCs derived from skin keratinocytes (NHEK). By introducing a four-factor Sendai virus transduction system, we successfully derived iPSCs from FTECs. To assess the differentiation capacity of iPSCs, we utilized embryoid body formation, revealing positive immunohistochemical staining for markers representing the three germ layers. In vivo tumorigenesis evaluation further validated the pluripotency of iPSCs, as evidenced by the formation of tumors in immunodeficient mice, with histological analysis confirming the presence of tissues from all three germ layers. Quantitative polymerase chain reaction (qPCR) analysis illuminated a sequential shift in gene expression, encompassing pluripotent, mesodermal, and intermediate mesoderm-related genes, during the iPSC differentiation process into FTECs. Notably, the introduction of WNT3A following intermediate mesoderm differentiation steered the cells toward a FTEC phenotype, supported by the expression of FTEC-related markers and the formation of tubule-like structures. In specific culture conditions, the expression of FTEC-related genes was comparable in FTECs derived from FTEC-iPSCs compared with those derived from NHEK-iPSCs. To conclude, our study successfully generated iPSCs from FTECs, demonstrating their capacity for FTEC differentiation. Furthermore, iPSCs originating from orthologous cell sources exhibited comparable differentiation capabilities. These findings hold promise for using iPSCs in modeling and investigating diseases associated with these specific cell types. |
| first_indexed | 2024-03-09T16:55:25Z |
| format | Article |
| id | doaj.art-1ba7e66768d6455a800e5a30e6b309f5 |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T16:55:25Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1ba7e66768d6455a800e5a30e6b309f52023-11-24T14:35:24ZengMDPI AGCells2073-44092023-11-011222263510.3390/cells12222635Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin OriginsYu-Hsun Chang0Kun-Chi Wu1Kai-Hung Wang2Dah-Ching Ding3Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 97004, TaiwanDepartment of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 97004, TaiwanDepartment of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 97004, TaiwanDepartment of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien 97004, TaiwanFallopian tube epithelial cells (FTECs) play a significant role in the development of high-grade serous ovarian cancer (HGSOC), but their utilization in in vitro experiments presents challenges. To address these limitations, induced pluripotent stem cells (iPSCs) have been employed as a potential solution, driven by the hypothesis that orthologous iPSCs may offer superior differentiation capabilities compared with their non-orthologous counterparts. Our objective was to generate iPSCs from FTECs, referred to as FTEC-iPSCs, and compare their differentiation potential with iPSCs derived from skin keratinocytes (NHEK). By introducing a four-factor Sendai virus transduction system, we successfully derived iPSCs from FTECs. To assess the differentiation capacity of iPSCs, we utilized embryoid body formation, revealing positive immunohistochemical staining for markers representing the three germ layers. In vivo tumorigenesis evaluation further validated the pluripotency of iPSCs, as evidenced by the formation of tumors in immunodeficient mice, with histological analysis confirming the presence of tissues from all three germ layers. Quantitative polymerase chain reaction (qPCR) analysis illuminated a sequential shift in gene expression, encompassing pluripotent, mesodermal, and intermediate mesoderm-related genes, during the iPSC differentiation process into FTECs. Notably, the introduction of WNT3A following intermediate mesoderm differentiation steered the cells toward a FTEC phenotype, supported by the expression of FTEC-related markers and the formation of tubule-like structures. In specific culture conditions, the expression of FTEC-related genes was comparable in FTECs derived from FTEC-iPSCs compared with those derived from NHEK-iPSCs. To conclude, our study successfully generated iPSCs from FTECs, demonstrating their capacity for FTEC differentiation. Furthermore, iPSCs originating from orthologous cell sources exhibited comparable differentiation capabilities. These findings hold promise for using iPSCs in modeling and investigating diseases associated with these specific cell types.https://www.mdpi.com/2073-4409/12/22/2635induced pluripotent stem cellfallopian tube epitheliumovarian cancerstem cellhigh-grade serous cancer |
| spellingShingle | Yu-Hsun Chang Kun-Chi Wu Kai-Hung Wang Dah-Ching Ding Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins Cells induced pluripotent stem cell fallopian tube epithelium ovarian cancer stem cell high-grade serous cancer |
| title | Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins |
| title_full | Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins |
| title_fullStr | Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins |
| title_full_unstemmed | Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins |
| title_short | Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins |
| title_sort | assessment of fallopian tube epithelium features derived from induced pluripotent stem cells of both fallopian tube and skin origins |
| topic | induced pluripotent stem cell fallopian tube epithelium ovarian cancer stem cell high-grade serous cancer |
| url | https://www.mdpi.com/2073-4409/12/22/2635 |
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