Retinoic acid signalling induces the differentiation of mouse fetal liver‐derived hepatic progenitor cells
Identifieur interne : 002863 ( Main/Exploration ); précédent : 002862; suivant : 002864Retinoic acid signalling induces the differentiation of mouse fetal liver‐derived hepatic progenitor cells
Auteurs : Jiayi Huang [République populaire de Chine, États-Unis] ; Yang Bi [République populaire de Chine, États-Unis] ; Gao-Hui Zhu [République populaire de Chine, États-Unis] ; Yun He [République populaire de Chine, États-Unis] ; Yuxi Su [République populaire de Chine, États-Unis] ; Bai-Cheng He [République populaire de Chine, États-Unis] ; Yi Wang [République populaire de Chine, États-Unis] ; Quan Kang [République populaire de Chine, États-Unis] ; Liang Chen [République populaire de Chine, États-Unis] ; Guo-Wei Zuo [République populaire de Chine, États-Unis] ; Qing Luo [République populaire de Chine, États-Unis] ; Qiong Shi [République populaire de Chine, États-Unis] ; Bing-Qiang Zhang [République populaire de Chine, États-Unis] ; Ailong Huang [République populaire de Chine] ; Lan Zhou [République populaire de Chine, États-Unis] ; Tao Feng [République populaire de Chine, États-Unis] ; Hue H. Luu [États-Unis] ; Rex C. Haydon [États-Unis] ; Tong-Chuan He [République populaire de Chine, États-Unis] ; Ni Tang [République populaire de Chine, États-Unis]Source :
- Liver International [ 1478-3223 ] ; 2009-11.
Abstract
Background: Hepatic progenitor cells (HPCs) can be isolated from fetal liver and extrahepatic tissues. Retinoic acid (RA) signalling plays an important role in development, although the role of RA signalling in liver‐specific progenitors is poorly understood. Aims: We sought to determine the role of RA in regulating hepatic differentiation. Methods: RNA was isolated from liver tissues of various developmental stages. Liver marker expression was assessed by reverse transcriptase‐polymerase chain reaction and immunofluorescence staining. Reversibly immortalized HPCs derived from mouse embryonic day 14.5 (E14.5) liver (aka, HP14.5) were established. Albumin promoter‐driven reporter (Alb‐GLuc) was used to monitor hepatic differentiation. Glycogen synthesis was assayed as a marker for terminal hepatic differentiation. Results: Retinoic acid receptor (RAR)‐α, retinoid X receptor (RXR)‐α and RXR‐γ expressed in E12.5 to postnatal day 28 liver samples. Expression of RAR‐β and RXR‐β was low perinatally, whereas RAR‐γ was undetectable in prenatal tissues and increased postnatally. Retinal dehydrogenase 1 and 2 (Raldh1 and Raldh2) were expressed in all tissues, while Raldh3 was weakly expressed in prenatal samples but was readily detected postnatally. Nuclear receptor corepressors were highly expressed in all tissues, while expression of nuclear co‐activators decreased in perinatal tissues and increased after birth. HP14.5 cells expressed high levels of early liver stem cell markers. Expression of RA signalling components and coregulators was readily detected in HP14.5. RA was shown to induce Alb‐GLuc activity and late hepatocyte markers. RA was further shown to induce glycogen synthesis in HP14.5 cells, an important function of mature hepatocytes. Conclusions: Our results strongly suggest that RA signalling may play an important role in regulating hepatic differentiation.
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DOI: 10.1111/j.1478-3231.2009.02111.x
Affiliations:
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Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Quan" sort="Kang, Quan" uniqKey="Kang Q" first="Quan" last="Kang">Quan Kang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Liang" sort="Chen, Liang" uniqKey="Chen L" first="Liang" last="Chen">Liang Chen</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Zuo, Guo Ei" sort="Zuo, Guo Ei" uniqKey="Zuo G" first="Guo-Wei" last="Zuo">Guo-Wei Zuo</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Qing" sort="Luo, Qing" uniqKey="Luo Q" first="Qing" last="Luo">Qing Luo</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Shi, Qiong" sort="Shi, Qiong" uniqKey="Shi Q" first="Qiong" last="Shi">Qiong Shi</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Bing Iang" sort="Zhang, Bing Iang" uniqKey="Zhang B" first="Bing-Qiang" last="Zhang">Bing-Qiang Zhang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Ailong" sort="Huang, Ailong" uniqKey="Huang A" first="Ailong" last="Huang">Ailong Huang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Lan" sort="Zhou, Lan" uniqKey="Zhou L" first="Lan" last="Zhou">Lan Zhou</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Feng, Tao" sort="Feng, Tao" uniqKey="Feng T" first="Tao" last="Feng">Tao Feng</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Luu, Hue H" sort="Luu, Hue H" uniqKey="Luu H" first="Hue H." last="Luu">Hue H. Luu</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Haydon, Rex C" sort="Haydon, Rex C" uniqKey="Haydon R" first="Rex C." last="Haydon">Rex C. Haydon</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="He, Tong Huan" sort="He, Tong Huan" uniqKey="He T" first="Tong-Chuan" last="He">Tong-Chuan He</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Ni" sort="Tang, Ni" uniqKey="Tang N" first="Ni" last="Tang">Ni Tang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL</wicri:regionArea><wicri:noRegion>IL</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Liver International</title><title level="j" type="alt">LIVER INTERNATIONAL</title><idno type="ISSN">1478-3223</idno><idno type="eISSN">1478-3231</idno><imprint><biblScope unit="vol">29</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1569">1569</biblScope><biblScope unit="page" to="1581">1581</biblScope><biblScope unit="page-count">13</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2009-11">2009-11</date></imprint><idno type="ISSN">1478-3223</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1478-3223</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Hepatic progenitor cells (HPCs) can be isolated from fetal liver and extrahepatic tissues. Retinoic acid (RA) signalling plays an important role in development, although the role of RA signalling in liver‐specific progenitors is poorly understood. Aims: We sought to determine the role of RA in regulating hepatic differentiation. Methods: RNA was isolated from liver tissues of various developmental stages. Liver marker expression was assessed by reverse transcriptase‐polymerase chain reaction and immunofluorescence staining. Reversibly immortalized HPCs derived from mouse embryonic day 14.5 (E14.5) liver (aka, HP14.5) were established. Albumin promoter‐driven reporter (Alb‐GLuc) was used to monitor hepatic differentiation. Glycogen synthesis was assayed as a marker for terminal hepatic differentiation. Results: Retinoic acid receptor (RAR)‐α, retinoid X receptor (RXR)‐α and RXR‐γ expressed in E12.5 to postnatal day 28 liver samples. Expression of RAR‐β and RXR‐β was low perinatally, whereas RAR‐γ was undetectable in prenatal tissues and increased postnatally. Retinal dehydrogenase 1 and 2 (Raldh1 and Raldh2) were expressed in all tissues, while Raldh3 was weakly expressed in prenatal samples but was readily detected postnatally. Nuclear receptor corepressors were highly expressed in all tissues, while expression of nuclear co‐activators decreased in perinatal tissues and increased after birth. HP14.5 cells expressed high levels of early liver stem cell markers. Expression of RA signalling components and coregulators was readily detected in HP14.5. RA was shown to induce Alb‐GLuc activity and late hepatocyte markers. RA was further shown to induce glycogen synthesis in HP14.5 cells, an important function of mature hepatocytes. Conclusions: Our results strongly suggest that RA signalling may play an important role in regulating hepatic differentiation.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Huang, Jiayi" sort="Huang, Jiayi" uniqKey="Huang J" first="Jiayi" last="Huang">Jiayi Huang</name></noRegion><name sortKey="Bi, Yang" sort="Bi, Yang" uniqKey="Bi Y" first="Yang" last="Bi">Yang Bi</name><name sortKey="Chen, Liang" sort="Chen, Liang" uniqKey="Chen L" first="Liang" last="Chen">Liang Chen</name><name sortKey="Feng, Tao" sort="Feng, Tao" uniqKey="Feng T" first="Tao" last="Feng">Tao Feng</name><name sortKey="He, Bai Heng" sort="He, Bai Heng" uniqKey="He B" first="Bai-Cheng" last="He">Bai-Cheng He</name><name sortKey="He, Tong Huan" sort="He, Tong Huan" uniqKey="He T" first="Tong-Chuan" last="He">Tong-Chuan He</name><name sortKey="He, Yun" sort="He, Yun" uniqKey="He Y" first="Yun" last="He">Yun He</name><name sortKey="Huang, Ailong" sort="Huang, Ailong" uniqKey="Huang A" first="Ailong" last="Huang">Ailong Huang</name><name sortKey="Kang, Quan" sort="Kang, Quan" uniqKey="Kang Q" first="Quan" last="Kang">Quan Kang</name><name sortKey="Luo, Qing" sort="Luo, Qing" uniqKey="Luo Q" first="Qing" last="Luo">Qing Luo</name><name sortKey="Shi, Qiong" sort="Shi, Qiong" uniqKey="Shi Q" first="Qiong" last="Shi">Qiong Shi</name><name sortKey="Su, Yuxi" sort="Su, Yuxi" uniqKey="Su Y" first="Yuxi" last="Su">Yuxi Su</name><name sortKey="Tang, Ni" sort="Tang, Ni" uniqKey="Tang N" first="Ni" last="Tang">Ni Tang</name><name sortKey="Wang, Yi" sort="Wang, Yi" uniqKey="Wang Y" first="Yi" last="Wang">Yi Wang</name><name sortKey="Zhang, Bing Iang" sort="Zhang, Bing Iang" uniqKey="Zhang B" first="Bing-Qiang" last="Zhang">Bing-Qiang Zhang</name><name sortKey="Zhou, Lan" sort="Zhou, Lan" uniqKey="Zhou L" first="Lan" last="Zhou">Lan Zhou</name><name sortKey="Zhu, Gao Ui" sort="Zhu, Gao Ui" uniqKey="Zhu G" first="Gao-Hui" last="Zhu">Gao-Hui Zhu</name><name sortKey="Zuo, Guo Ei" sort="Zuo, Guo Ei" uniqKey="Zuo G" first="Guo-Wei" last="Zuo">Guo-Wei Zuo</name></country><country name="États-Unis"><noRegion><name sortKey="Huang, Jiayi" sort="Huang, Jiayi" uniqKey="Huang J" first="Jiayi" last="Huang">Jiayi Huang</name></noRegion><name sortKey="Bi, Yang" sort="Bi, Yang" uniqKey="Bi Y" first="Yang" last="Bi">Yang Bi</name><name sortKey="Chen, Liang" sort="Chen, Liang" uniqKey="Chen L" first="Liang" last="Chen">Liang Chen</name><name sortKey="Feng, Tao" sort="Feng, Tao" uniqKey="Feng T" first="Tao" last="Feng">Tao Feng</name><name sortKey="Haydon, Rex C" sort="Haydon, Rex C" uniqKey="Haydon R" first="Rex C." last="Haydon">Rex C. Haydon</name><name sortKey="He, Bai Heng" sort="He, Bai Heng" uniqKey="He B" first="Bai-Cheng" last="He">Bai-Cheng He</name><name sortKey="He, Tong Huan" sort="He, Tong Huan" uniqKey="He T" first="Tong-Chuan" last="He">Tong-Chuan He</name><name sortKey="He, Yun" sort="He, Yun" uniqKey="He Y" first="Yun" last="He">Yun He</name><name sortKey="Kang, Quan" sort="Kang, Quan" uniqKey="Kang Q" first="Quan" last="Kang">Quan Kang</name><name sortKey="Luo, Qing" sort="Luo, Qing" uniqKey="Luo Q" first="Qing" last="Luo">Qing Luo</name><name sortKey="Luu, Hue H" sort="Luu, Hue H" uniqKey="Luu H" first="Hue H." last="Luu">Hue H. Luu</name><name sortKey="Shi, Qiong" sort="Shi, Qiong" uniqKey="Shi Q" first="Qiong" last="Shi">Qiong Shi</name><name sortKey="Su, Yuxi" sort="Su, Yuxi" uniqKey="Su Y" first="Yuxi" last="Su">Yuxi Su</name><name sortKey="Tang, Ni" sort="Tang, Ni" uniqKey="Tang N" first="Ni" last="Tang">Ni Tang</name><name sortKey="Wang, Yi" sort="Wang, Yi" uniqKey="Wang Y" first="Yi" last="Wang">Yi Wang</name><name sortKey="Zhang, Bing Iang" sort="Zhang, Bing Iang" uniqKey="Zhang B" first="Bing-Qiang" last="Zhang">Bing-Qiang Zhang</name><name sortKey="Zhou, Lan" sort="Zhou, Lan" uniqKey="Zhou L" first="Lan" last="Zhou">Lan Zhou</name><name sortKey="Zhu, Gao Ui" sort="Zhu, Gao Ui" uniqKey="Zhu G" first="Gao-Hui" last="Zhu">Gao-Hui Zhu</name><name sortKey="Zuo, Guo Ei" sort="Zuo, Guo Ei" uniqKey="Zuo G" first="Guo-Wei" last="Zuo">Guo-Wei Zuo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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