The diversity and plasticity of adult hepatic progenitor cells and their niche - PubMed (original) (raw)

Review

. 2017 Sep;37(9):1260-1271.

doi: 10.1111/liv.13377. Epub 2017 Feb 23.

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Review

The diversity and plasticity of adult hepatic progenitor cells and their niche

Jiamei Chen et al. Liver Int. 2017 Sep.

Abstract

The liver is a unique organ for homoeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several facultative hepatic progenitor cell compartments. Newly identified pericentral stem/progenitor cells residing around the central vein is responsible for maintaining hepatocyte homoeostasis in the uninjured liver. In addition, hepatic progenitor cells have been reported to contribute to liver fibrosis and cancers. What drives liver homoeostasis, regeneration and diseases is determined by the physiological and pathological conditions, and especially the hepatic progenitor cell niches which influence the fate of hepatic progenitor cells. The hepatic progenitor cell niches are special microenvironments consisting of different cell types, releasing growth factors and cytokines and receiving signals, as well as the extracellular matrix (ECM) scaffold. The hepatic progenitor cell niches maintain and regulate stem cells to ensure organ homoeostasis and regeneration. In recent studies, more evidence has been shown that hepatic cells such as hepatocytes, cholangiocytes or myofibroblasts can be induced to be oval cell-like state through transitions under some circumstance, those transitional cell types as potential liver-resident progenitor cells play important roles in liver pathophysiology. In this review, we describe and update recent advances in the diversity and plasticity of hepatic progenitor cell and their niches and discuss evidence supporting their roles in liver homoeostasis, regeneration, fibrosis and cancers.

Keywords: hepatic stem/progenitor cells; liver homoeostasis; liver regeneration; stem cell niche.

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Conflict of interest statement

Conflict of interest

The authors do not have any disclosures to report.

Figures

Figure 1

Figure 1. Model of the adult hepatic stem/progenitor cell niche

(a): In the uninjured liver the Wnt-responsive stem cell population resides around the central vein. These cells self-renew and differentiate into hepatocytes and replace other hepatocytes for liver homeostasis. (b and c): In the injured liver, the canal of Herring (b) and the space of Disse (c) can provide a niches for adult HPCs. These niches are composed of different cell types, ECM components, growth factors and cytokines released by the niche cells and signaling pathways that help to maintain the characteristics of adult HPCs and control activation and proliferation, and govern differentiation fate decisions.

Figure 2

Figure 2. A schematic illustration shows that the activation and transition, proliferation and differentiation of the adult HPCs are determined by the factors and signals received

Resident adult hepatic/stem cells are activated from their niche after receiving certain factors and signals or transitioned from hepatocytes or myofibroblasts by ductal metaplasia or MET (Left column); and proliferated (Central column); then differentiated towards hepatocytes by the activation of Wnt/β-catenin signaling and the up-regulation of Wnt2 and Wnt9b, differentiated towards cholangiocytes by the activation of Notch signaling pathway, trans-differentiated into hepatic stellate cells by the up-regulation of TGF-β and CTGF, trans-differentiated into myofibroblasts by the up-regulation of Fox1 and TGF-β and the activation of non-canonial Wnt signaling pathway, and transformed into tumor-initiating cells by the up-regulation of TGF-β and Bmil and the activation of Wnt/β-catenin signaling pathway (Right column). Abbreviations: MET, mesenchymal-epithelial transitions; HGF: hepatocyte growth factor; TGF-β: transforming growth factor-β; EGF, epidermal growth factor; aFGF, acidic fibroblast growth factor; TNF, tumor necrosis factor; IL-6: interleukin-6; LT-β: lymphotoxin β; LT-α: lymphotoxin α: IFN-α: interferon α; IFN-γ: interferon γ; TWEAK: TNF-like weak inducer of apoptosis; CTGF: connective tissue growth factor.

Figure 3

Figure 3. A schematic illustration of the involvement of adult hepatic progenitor cells in liver disease

Resident or transitional hepatic progenitor cells (HPC) will be differentiated towards hepatocytes or cholangiocytes under liver injury conditions such as in acute/chronic viral hepatitis, non-alcoholic and alcoholic steatohepatitis, or in primary biliary cholangitis, primary sclerosing cholangitis. Under some circumstance, HPCs can be trans-differentiated into myofibroblasts and/or hepatic stellate cells to contribute to the development and progression of liver fibrosis, and can be transformed into tumor initiating cells to initiate and sustain hepatocellular carcinoma, or cholangiocarcinoma, or both.

References

    1. BOULTER L, LU WY, FORBES SJ. Differentiation of progenitors in the liver: a matter of local choice. The Journal of clinical investigation. 2013;123(5):1867–73. -PMC -PubMed
    1. MARSHALL A, RUSHBROOK S, DAVIES SE, et al. Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology. 2005;128(1):33–42. -PubMed
    1. ROSKAMS T, YANG SQ, KOTEISH A, et al. Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. Am J Pathol. 2003;163(4):1301–11. -PMC -PubMed
    1. DE VOSR, DESMET V. Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction. The American journal of pathology. 1992;140(6):1441–50. -PMC -PubMed
    1. FARBER E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3′-methyl-4-dimethylaminoazobenzene. Cancer Res. 1956;16(2):142–8. -PubMed

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