Retinoic acid signalling induces the differentiation of mouse fetal liver‐derived hepatic progenitor cells

作者：Jiayi Huang, Yang Bi, Gaohui Zhu, Yun He, Yuxi Su, Bai‐Cheng He, Yi Wang, Quan Kang, Liang Chen, Guowei Zuo, Qing Luo, Qiong Shi, Bingqiang Zhang, Ailong Huang, Lan Zhou, Tao Feng, Hue H. Luu, Rex C. Haydon, Tong‐Chuan He, Ni Tang · 发表于：Liver International · 年份：2009 · DOI：10.1111/j.1478-3231.2009.02111.x · 被引用次数：86 · 研究领域：Retinoids in leukemia and cellular processes、Liver physiology and pathology、Growth Hormone and Insulin-like Growth Factors

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 ...