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

Liver International - Tập 29 Số 10 - Trang 1569-1581 - 2009
Jiayi Huang1,2,3, Yang Bi1,2,3, Zhu Gao2,3, Yun He2,3, Yuxi Su2,3, Bai‐Cheng He2,3, Yi Wang2,3, Quan Kang2,3, Liang Chen2,3, Guowei Zuo2,3, Qing Luo2,3, Qiong Shi2,3, Bingqiang Zhang2,3, Ailong Huang2, Lan Zhou2,3, Tao Feng2,3, Hue H. Luu3, Rex C. Haydon3, Tong‐Chuan He2,3, Ni Tang2,3
1These authors contributed equally to the work
2Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, The Affiliated Hospitals of Chongqing Medical University, Chongqing, China
3Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA

Tóm tắt

AbstractBackground: 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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Tài liệu tham khảo

Zaret KS., 2002, Regulatory phases of early liver development, paradigms of organogenesis, 3, 499

Zaret KS., 2008, Genetic programming of liver and pancreas progenitors, lessons for stem-cell differentiation, 9, 329

10.1126/science.1161431

10.1002/hep.21651

10.1007/s00441-007-0483-6

10.1016/S0925-4773(02)00338-6

10.1016/j.bbadis.2007.12.004

Walkup MH, 2006, Hepatic stem cells, in search of, 24, 1833

10.1634/stemcells.2006-0036

Kitisin K, 2007, Hepatocellular stem cells, Cancer Biomark, 3, 251, 10.3233/CBM-2007-34-509

10.1111/j.1582-4934.2006.tb00422.x

10.1016/j.semcdb.2007.09.016

10.1053/jhep.2002.36123

10.3727/000000001783986945

10.1016/j.yexcr.2007.05.020

10.1152/ajpgi.00187.2007

10.1016/j.cell.2008.09.002

Niederreither K, 2008, Retinoic acid in development, towards an integrated view, 9, 541

10.1038/nm1587

Mark M, 2006, Function of retinoid nuclear receptors, lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis, 46, 451

Chawla A, 2001, Nuclear receptors and lipid physiology, opening the X-files, 294, 1866

10.1242/dev.129.9.2271

10.1038/415187a

Collingwood TN, 1999, Nuclear receptors, coactivators, corepressors and chromatin remodeling in the control of transcription, 23, 255

10.1073/pnas.93.17.8971

10.1038/sj.onc.1209558

10.3748/wjg.v12.i39.6261

10.1074/jbc.M407810200

10.1038/labinvest.2008.98

10.1002/jcb.10744

10.1074/jbc.M403344200

10.1128/MCB.26.8.2955-2964.2006

10.1111/j.1582-4934.2008.00569.x

10.1089/scd.2008.0130

10.1038/sj.gt.3302298

10.1007/s10585-005-0365-9

10.1074/jbc.M806389200

10.1084/jem.20040394

Hirano K, 2008, Expression of stem cell factor (SCF), a KIT ligand, in gastrointestinal stromal tumors (GISTs), a potential marker for tumor proliferation, 204, 799

10.1016/j.cellbi.2008.07.017

Levesque E, 2007, Regulation of the UGT1A1 bilirubin‐conjugating pathway, role of a new splicing event at the UGT1A locus, 45, 128

10.1053/jhep.2001.21900

10.1016/j.ydbio.2007.09.014

10.1101/gad.8.9.1007

10.1002/dvdy.10455

10.1093/nar/22.11.2126

10.1128/MCB.21.21.7320-7330.2001

10.1006/excr.1999.4512

10.1006/excr.1995.1065

Hu Z, 1994, Hepatic regeneration in vitamin A‐deficient rats, changes in the expression of transforming growth factor alpha/epidermal growth factor receptor and retinoic acid receptors alpha and beta, 5, 503

10.1016/j.bcp.2008.02.030

10.1093/carcin/bgh221

Park BH, 2001, Peroxisome proliferator‐activated receptors, roles in tumorigenesis and chemoprevention in human cancer, 13, 78

Freemantle SJ, 2003, Retinoids in cancer therapy and chemoprevention, promise meets resistance, 22, 7305

Karamouzis MV, 2007, The molecular basis of retinoids' use in breast cancer chemoprevention, Cell Oncol, 29, 183

Lotan R., 1995, Retinoids and apoptosis, implications for cancer chemoprevention and therapy, 87, 1655

10.1096/fasebj.10.9.8801164

10.2174/1568009043333023

10.2741/1425

10.1016/S1040-8428(01)00144-5

Verma AK., 2003, Retinoids in chemoprevention of cancer, J Biol Regul Homeost Agents, 17, 92

10.1016/S1359-6446(02)02526-6

10.1146/annurev.nu.15.070195.000551

10.1146/annurev.pharmtox.39.1.399

10.1016/S0168-9525(99)01710-2

Haydon RC, 2007, Osteosarcoma and osteoblastic differentiation, a new perspective on oncogenesis, 454, 237

Haydon RC, 2002, Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma, Clin Cancer Res, 8, 1288

10.1002/jcb.21530

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Liver International

Tập 29 Số 10

1569-1581

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