Top

Journal of Hepato-Biliary-Pancreatic Sciences

Published in:

01-11-2012 | Topics

Characteristics of hepatic stem/progenitor cells in the fetal and adult liver

Authors: Hiroyuki Koike, Hideki Taniguchi

Published in: Journal of Hepato-Biliary-Pancreatic Sciences | Issue 6/2012

Abstract

Background

The liver is an essential organ that maintains vital activity through its numerous important functions. It has a unique capability of fully regenerating after injury. Regulating a balance between self-renewal and differentiation of hepatic stem cells that are resources for functional mature liver cells is required for maintenance of tissue homeostasis.

Methods

This review describes the characteristics of hepatic stem/progenitor cells and the regulatory mechanism of their self-renewal and differentiation capacity.

Results

In liver organogenesis, undifferentiated hepatic stem/progenitor cells expand their pool by repeated self-renewal in the early stage of liver development and then differentiate into two different types of cell lineage, namely hepatocytes and cholangiocytes. Liver development is regulated by expression of stem cell transcription factors in a complex multistep process. Recent studies suggest that stem cells are maintained by integrative regulation of gene expression patterns related to self-renewal and differentiation by epigenetic mechanisms such as histone modification and DNA methylation.

Conclusions

Analysis of the proper regulatory mechanism of hepatic stem/progenitor cells is important for regenerative medicine that utilizes hepatic stem cells and for preventing liver cancer through clarification of the carcinogenetic mechanism involved in stem cell system failure.

Quante M, Wang TC. Stem cells in gastroenterology and hepatology. Nat Rev Gastroenterol Hepatol. 2009;6(12):724–37. doi:10.1038/nrgastro.2009.195.PubMedCrossRef

Turner R, Lozoya O, Wang Y, Cardinale V, Gaudio E, Alpini G, et al. Human hepatic stem cell and maturational liver lineage biology. Hepatology. 2011;53(3):1035–45. doi:10.1002/hep.24157.PubMedCrossRef

Yeung TM, Chia LA, Kosinski CM, Kuo CJ. Regulation of self-renewal and differentiation by the intestinal stem cell niche. Cell Mol Life Sci. 2011;68(15):2513–23. doi:10.1007/s00018-011-0687-5.PubMedCrossRef

Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, et al. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell. 2011;8(1):59–71. doi:10.1016/j.stem.2010.11.028.PubMedCrossRef

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100(7):3983–8. doi:10.1073/pnas.0530291100.PubMedCrossRef

Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 2008;68(5):1451–61. doi:10.1158/0008-5472.CAN-07-6013.PubMedCrossRef

Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423(6938):409–14. doi:10.1038/nature01593.PubMedCrossRef

Po A, Ferretti E, Miele E, De Smaele E, Paganelli A, Canettieri G, et al. Hedgehog controls neural stem cells through p53-independent regulation of Nanog. EMBO J. 2010;29(15):2646–58. doi:10.1038/emboj.2010.131.PubMedCrossRef

Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, et al. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol. 2005;6(3):314–22. doi:10.1038/ni1164.PubMedCrossRef

10.

Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006;125(2):315–26. doi:10.1016/j.cell.2006.02.041.PubMedCrossRef

11.

Berdasco M, Esteller M. DNA methylation in stem cell renewal and multipotency. Stem Cell Res Ther. 2011;2(5):42. doi:10.1186/scrt83.PubMedCrossRef

12.

Shiojiri N. The origin of intrahepatic bile duct cells in the mouse. J Embryol Exp Morphol. 1984;79:25–39.PubMed

13.

Matsumoto K, Yoshitomi H, Rossant J, Zaret KS. Liver organogenesis promoted by endothelial cells prior to vascular function. Science. 2001;294(5542):559–63. doi:10.1126/science.1063889.PubMedCrossRef

14.

Lemaigre F, Zaret KS. Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev. 2004;14(5):582–90. doi:10.1016/j.gde.2004.08.004.PubMedCrossRef

15.

Strick-Marchand H, Weiss MC. Inducible differentiation and morphogenesis of bipotential liver cell lines from wild-type mouse embryos. Hepatology. 2002;36(4 Pt 1):794–804. doi:10.1053/jhep.2002.36123.PubMed

16.

Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res. 1991;51(10):2611–20.PubMed

17.

Shiojiri N. Development and differentiation of bile ducts in the mammalian liver. Microsc Res Tech. 1997;39(4):328–35. doi:10.1002/(SICI)1097-0029(19971115)39:4<328:AID-JEMT3>3.0.CO;2-D.PubMedCrossRef

18.

Jelnes P, Santoni-Rugiu E, Rasmussen M, Friis SL, Nielsen JH, Tygstrup N, et al. Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration. Hepatology. 2007;45(6):1462–70. doi:10.1002/hep.21569.PubMedCrossRef

19.

Okada K, Kamiya A, Ito K, Yanagida A, Ito H, Kondou H, et al. Prospective isolation and characterization of bipotent progenitor cells in early mouse liver development. Stem Cells Dev. 2011;. doi:10.1089/scd.2011.0229.

20.

Kamiya A, Kakinuma S, Yamazaki Y, Nakauchi H. Enrichment and clonal culture of progenitor cells during mouse postnatal liver development in mice. Gastroenterology. 2009;137(3):1114–26, 26 e1–14. doi:10.1053/j.gastro.2009.06.001.

21.

Tanaka M, Okabe M, Suzuki K, Kamiya Y, Tsukahara Y, Saito S, et al. Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: drastic change of EpCAM expression during liver development. Mech Dev. 2009;126(8–9):665–76. doi:10.1016/j.mod.2009.06.939.PubMedCrossRef

22.

Engelhardt NV, Factor VM, Medvinsky AL, Baranov VN, Lazareva MN, Poltoranina VS. Common antigen of oval and biliary epithelial cells (A6) is a differentiation marker of epithelial and erythroid cell lineages in early development of the mouse. Differentiation. 1993;55(1):19–26.PubMedCrossRef

23.

Ueberham E, Aigner T, Ueberham U, Gebhardt R. E-cadherin as a reliable cell surface marker for the identification of liver specific stem cells. J Mol Histol. 2007;38(4):359–68. doi:10.1007/s10735-007-9098-1.PubMedCrossRef

24.

Suzuki A, Sekiya S, Onishi M, Oshima N, Kiyonari H, Nakauchi H, et al. Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver. Hepatology. 2008;48(6):1964–78. doi:10.1002/hep.22558.PubMedCrossRef

25.

Yang L, Faris RA, Hixson DC. Characterization of a mature bile duct antigen expressed on a subpopulation of biliary ductular cells but absent from oval cells. Hepatology. 1993;18(2):357–66.PubMed

26.

Kakinuma S, Ohta H, Kamiya A, Yamazaki Y, Oikawa T, Okada K, et al. Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver. J Hepatol. 2009;51(1):127–38. doi:10.1016/j.jhep.2009.02.033.PubMedCrossRef

27.

Tanaka M, Miyajima A. Identification and isolation of adult liver stem/progenitor cells. Methods Mol Biol. 2012;826:25–32. doi:10.1007/978-1-61779-468-1_3.PubMedCrossRef

28.

Mansuroglu T, Ramadori P, Dudas J, Malik I, Hammerich K, Fuzesi L, et al. Expression of stem cell factor and its receptor c-Kit during the development of intrahepatic cholangiocarcinoma. Lab Invest. 2009;89(5):562–74. doi:10.1038/labinvest.2009.15.PubMedCrossRef

29.

Petersen BE, Grossbard B, Hatch H, Pi L, Deng J, Scott EW. Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers. Hepatology. 2003;37(3):632–40. doi:10.1053/jhep.2003.50104.PubMedCrossRef

30.

Hu Z, Evarts RP, Fujio K, Marsden ER, Thorgeirsson SS. Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development in the rat. Am J Pathol. 1993;142(6):1823–30.PubMed

31.

Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, et al. Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Development. 2009;136(11):1951–60. doi:10.1242/dev.031369.PubMedCrossRef

32.

Hixson DC, Chapman L, McBride A, Faris R, Yang L. Antigenic phenotypes common to rat oval cells, primary hepatocellular carcinomas and developing bile ducts. Carcinogenesis. 1997;18(6):1169–75.PubMedCrossRef

33.

Jin C, Samuelson L, Cui CB, Sun Y, Gerber DA. MAPK/ERK and Wnt/beta-catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells. Biochem Biophys Res Commun. 2011;409(4):803–7. doi:10.1016/j.bbrc.2011.05.094.PubMedCrossRef

34.

Suzuki A, Zheng Y, Kondo R, Kusakabe M, Takada Y, Fukao K, et al. Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology. 2000;32(6):1230–9. doi:10.1053/jhep.2000.20349.PubMedCrossRef

35.

Suzuki A, Zheng YW, Kaneko S, Onodera M, Fukao K, Nakauchi H, et al. Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J Cell Biol. 2002;156(1):173–84. doi:10.1083/jcb.200108066.PubMedCrossRef

36.

Tanimizu N, Nishikawa M, Saito H, Tsujimura T, Miyajima A. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci. 2003;116(Pt 9):1775–86.PubMedCrossRef

37.

Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, et al. Human hepatic stem cells from fetal and postnatal donors. J Exp Med. 2007;204(8):1973–87. doi:10.1084/jem.20061603.PubMedCrossRef

38.

Theise ND, Saxena R, Portmann BC, Thung SN, Yee H, Chiriboga L, et al. The canals of Hering and hepatic stem cells in humans. Hepatology. 1999;30(6):1425–33. doi:10.1002/hep.510300614.PubMedCrossRef

39.

Li J, Ning G, Duncan SA. Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha. Genes Dev. 2000;14(4):464–74.PubMed

40.

Zong Y, Panikkar A, Xu J, Antoniou A, Raynaud P, Lemaigre F, et al. Notch signaling controls liver development by regulating biliary differentiation. Development. 2009;136(10):1727–39. doi:10.1242/dev.029140.PubMedCrossRef

41.

Sekiya S, Suzuki A. Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature. 2011;475(7356):390–3. doi:10.1038/nature10263.PubMedCrossRef

42.

Swenson ES. Direct conversion of mouse fibroblasts to hepatocyte-like cells using forced expression of endodermal transcription factors. Hepatology. 2012;55(1):316–8. doi:10.1002/hep.24717.PubMedCrossRef

43.

Spee B, Carpino G, Schotanus BA, Katoonizadeh A, Vander Borght S, Gaudio E, et al. Characterisation of the liver progenitor cell niche in liver diseases: potential involvement of Wnt and Notch signalling. Gut. 2010;59(2):247-57. doi:10.1136/gut.2009.188367.

44.

Hirose Y, Itoh T, Miyajima A. Hedgehog signal activation coordinates proliferation and differentiation of fetal liver progenitor cells. Exp Cell Res. 2009;315(15):2648–57. doi:10.1016/j.yexcr.2009.06.018.PubMedCrossRef

45.

Tan X, Yuan Y, Zeng G, Apte U, Thompson MD, Cieply B, et al. Beta-catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development. Hepatology. 2008;47(5):1667–79. doi:10.1002/hep.22225.PubMedCrossRef

46.

Zhou D, Zhang Y, Pan YX, Chen H. Dickkopf homolog 1, a Wnt signaling antagonist, is transcriptionally up-regulated via an ATF4-independent and MAPK/ERK-dependent pathway following amino acid deprivation. Biochim Biophys Acta. 2011;1809(7):306–15. doi:10.1016/j.bbagrm.2011.05.016.PubMedCrossRef

47.

Tanimizu N, Miyajima A. Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors. J Cell Sci. 2004;117(Pt 15):3165–74. doi:10.1242/jcs.01169.PubMedCrossRef

48.

Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41–5. doi:10.1038/47412.PubMedCrossRef

49.

Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423(6937):302–5. doi:10.1038/nature01587.PubMedCrossRef

50.

Roman-Trufero M, Mendez-Gomez HR, Perez C, Hijikata A, Fujimura Y, Endo T, et al. Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B. Stem Cells. 2009;27(7):1559–70. doi:10.1002/stem.82.PubMedCrossRef

51.

Juan AH, Derfoul A, Feng X, Ryall JG, Dell’Orso S, Pasut A, et al. Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells. Genes Dev. 2011;25(8):789–94. doi:10.1101/gad.2027911.PubMedCrossRef

52.

Stock JK, Giadrossi S, Casanova M, Brookes E, Vidal M, Koseki H, et al. Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat Cell Biol. 2007;9(12):1428–35. doi:10.1038/ncb1663.PubMedCrossRef

53.

Xu CR, Cole PA, Meyers DJ, Kormish J, Dent S, Zaret KS. Chromatin “prepattern” and histone modifiers in a fate choice for liver and pancreas. Science. 2011;332(6032):963–6. doi:10.1126/science.1202845.PubMedCrossRef

54.

Aoki R, Chiba T, Miyagi S, Negishi M, Konuma T, Taniguchi H, et al. The polycomb group gene product Ezh2 regulates proliferation and differentiation of murine hepatic stem/progenitor cells. J Hepatol. 2010;52(6):854–63. doi:10.1016/j.jhep.2010.01.027.PubMedCrossRef

55.

Kubicek S, Gilbert JC, Fomina-Yadlin D, Gitlin AD, Yuan Y, Wagner FF, et al. Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells. Proc Natl Acad Sci USA. 2012;. doi:10.1073/pnas.1201079109.

56.

Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132(7):2542–56. doi:10.1053/j.gastro.2007.04.025.PubMedCrossRef

57.

Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology. 2007;133(3):937–50. doi:10.1053/j.gastro.2007.06.016.PubMedCrossRef

Title: Characteristics of hepatic stem/progenitor cells in the fetal and adult liver
Authors: Hiroyuki Koike
Hideki Taniguchi
Publication date: 01-11-2012
Publisher: Springer Japan
Published in: Journal of Hepato-Biliary-Pancreatic Sciences / Issue 6/2012
Print ISSN: 1868-6974
Electronic ISSN: 1868-6982
DOI: https://doi.org/10.1007/s00534-012-0544-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Characteristics of hepatic stem/progenitor cells in the fetal and adult liver

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2012

Erratum to: Human equilibrative nucleoside transporter 1 level does not predict prognosis in pancreatic cancer patients treated with neoadjuvant chemoradiation including gemcitabine

Outcomes of ultrasound-guided percutaneous argon-helium cryoablation of hepatocellular carcinoma

Diagnostic yield of endoscopic retrograde cholangiography and of EUS-guided fine needle aspiration sampling in gallbladder carcinomas

Recent advances in cancer stem cell research for cholangiocarcinoma

Image-guided hepatopancreatobiliary surgery using near-infrared fluorescent light

Area between the hepatic and heart curves of 99mTc-galactosyl-human serum albumin scintigraphy represents liver function and disease progression for preoperative evaluation in hepatocellular carcinoma patients