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)-alpha, retinoid X receptor (RXR)-alpha and RXR-gamma expressed in E12.5 to postnatal day 28 liver samples. Expression of RAR-beta and RXR-beta was low perinatally, whereas RAR-gamma 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.
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)-alpha, retinoid X receptor (RXR)-alpha and RXR-gamma expressed in E12.5 to postnatal day 28 liver samples. Expression of RAR-beta and RXR-beta was low perinatally, whereas RAR-gamma 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.
Authors: Gaurav Luther; Richard Rames; Eric R Wagner; Gaohui Zhu; Qing Luo; Yang Bi; Stephanie H Kim; Jian-Li Gao; Enyi Huang; Ke Yang; Linyuan Wang; Xing Liu; Mi Li; Ning Hu; Yuxi Su; Xiaoji Luo; Liang Chen; Jinyong Luo; Rex C Haydon; Hue H Luu; Lan Zhou; Tong-Chuan He Journal: Trends Cancer Res Date: 2010
Authors: Xiaojun Wang; Jing Cui; Bing-Qiang Zhang; Hongyu Zhang; Yang Bi; Quan Kang; Ning Wang; Ping Bie; Zhanyu Yang; Huaizhi Wang; Xiangde Liu; Rex C Haydon; Hue H Luu; Ni Tang; Jiahong Dong; Tong-Chuan He Journal: J Biomed Mater Res A Date: 2013-06-04 Impact factor: 4.396
Authors: Ling Zhao; Linjuan Huang; Jing Zhang; Jiaming Fan; Fang He; Xia Zhao; Hao Wang; Qing Liu; Deyao Shi; Na Ni; William Wagstaff; Mikhail Pakvasa; Kai Fu; Andrew B Tucker; Connie Chen; Russell R Reid; Rex C Haydon; Hue H Luu; Le Shen; Hongbo Qi; Tong-Chuan He Journal: Am J Transl Res Date: 2020-12-15 Impact factor: 4.060