Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver
Background/Aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to esta...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2014-10-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/366340 |
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| author | Yang Bi Yun He Jiayi Huang Yuxi Su Gao-Hui Zhu Yi Wang Min Qiao Bing-Qiang Zhang Hongyu Zhang Zhongliang Wang Wei Liu Jing Cui Quan Kang Zhonglin Zhang Youlin Deng Ruifang Li Qian Zhang Ke Yang Hue H. Luu Rex C. Haydon Tong-Chuan He Ni Tang |
| author_facet | Yang Bi Yun He Jiayi Huang Yuxi Su Gao-Hui Zhu Yi Wang Min Qiao Bing-Qiang Zhang Hongyu Zhang Zhongliang Wang Wei Liu Jing Cui Quan Kang Zhonglin Zhang Youlin Deng Ruifang Li Qian Zhang Ke Yang Hue H. Luu Rex C. Haydon Tong-Chuan He Ni Tang |
| author_sort | Yang Bi |
| collection | DOAJ |
| description | Background/Aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver. Methods and Results: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk) and hepatocyte markers (AFP, Alb and ApoB). Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks. Conclusions: We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation. |
| first_indexed | 2024-12-10T06:29:08Z |
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| id | doaj.art-75ac7a75f30b4424811ba63eab28021f |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T06:29:08Z |
| publishDate | 2014-10-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-75ac7a75f30b4424811ba63eab28021f2022-12-22T01:59:07ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-10-013441318133810.1159/000366340366340Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic LiverYang BiYun HeJiayi HuangYuxi SuGao-Hui ZhuYi WangMin QiaoBing-Qiang ZhangHongyu ZhangZhongliang WangWei LiuJing CuiQuan KangZhonglin ZhangYoulin DengRuifang LiQian ZhangKe YangHue H. LuuRex C. HaydonTong-Chuan HeNi TangBackground/Aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver. Methods and Results: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk) and hepatocyte markers (AFP, Alb and ApoB). Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks. Conclusions: We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation.http://www.karger.com/Article/FullText/366340Reversible immortalizationSV40 large T antigenHepatic differentiationHepatic progenitor cellsHepatocyte transplantationLiver stem cells |
| spellingShingle | Yang Bi Yun He Jiayi Huang Yuxi Su Gao-Hui Zhu Yi Wang Min Qiao Bing-Qiang Zhang Hongyu Zhang Zhongliang Wang Wei Liu Jing Cui Quan Kang Zhonglin Zhang Youlin Deng Ruifang Li Qian Zhang Ke Yang Hue H. Luu Rex C. Haydon Tong-Chuan He Ni Tang Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver Cellular Physiology and Biochemistry Reversible immortalization SV40 large T antigen Hepatic differentiation Hepatic progenitor cells Hepatocyte transplantation Liver stem cells |
| title | Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver |
| title_full | Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver |
| title_fullStr | Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver |
| title_full_unstemmed | Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver |
| title_short | Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver |
| title_sort | functional characteristics of reversibly immortalized hepatic progenitor cells derived from mouse embryonic liver |
| topic | Reversible immortalization SV40 large T antigen Hepatic differentiation Hepatic progenitor cells Hepatocyte transplantation Liver stem cells |
| url | http://www.karger.com/Article/FullText/366340 |
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