Zaret K S, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science, 2008

Epigenetics and Progenitor Cells Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Science (Impact Factor: 33.61). 01/2009; 322(5907):1490-4. DOI: 10.1126/science.1161431
Source: PubMed


Liver and pancreas progenitors develop from endoderm cells in the embryonic foregut. Shortly after their specification, liver and pancreas progenitors rapidly acquire markedly different cellular functions and regenerative capacities. These changes are elicited by inductive signals and genetic regulatory factors that are highly conserved among vertebrates. Interest in the development and regeneration of the organs has been fueled by the intense need for hepatocytes and pancreatic beta cells in the therapeutic treatment of liver failure and type I diabetes. Studies in diverse model organisms have revealed evolutionarily conserved inductive signals and transcription factor networks that elicit the differentiation of liver and pancreatic cells and provide guidance for how to promote hepatocyte and beta cell differentiation from diverse stem and progenitor cell types.

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Available from: Markus Grompe, Jun 15, 2015
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    • "However, given the ability of progenitor-derived cells to express characteristic hepatocyte genes in vitro, we surmised that this population contained (and retained) meaningful differentiation potential. The pancreas and liver share developmental origins (Kawaguchi, 2013; Zaret and Grompe, 2008) and the ductal epithelial cells in these adult organs have similar functions and morphological appearance. The appearance of hepatocyte-like cells in the pancreata of rats fed a copper-deficient diet (Rao et al., 1986) illustrates the potential for transdifferentiation between cell types from these organs. "

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    • "The EHBD system, the liver and the ventral pancreas develop from the posterior ventral foregut endoderm (Shiojiri, 1997; Zaret and Grompe, 2008; Tremblay and Zaret, 2005). However, the cell-intrinsic factors responsible for IHBD and EHBD system specification are unclear. "
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    ABSTRACT: There are currently no reports of identification of stem cells in human gallbladder. The differences between human gallbladder and intrahepatic bile duct (IHBD) cells have also not been explored. The goals of this study were to evaluate if human fetal gallbladder contains a candidate stem cell population and if fetal gallbladder cells are distinct from fetal IHBD cells. We found that EpCAM+CD44+CD13+ cells represent the cell population most enriched for clonal self-renewal from primary gallbladder. Primary EpCAM+CD44+CD13+ cells gave rise to EpCAM+CD44+CD13+ and EpCAM+CD44+CD13- cells in vitro, and gallbladder cells expanded in vitro exhibited short-term engraftment in vivo. Last, we found that CD13, CD227, CD66, CD26 and CD49b were differentially expressed between gallbladder and IHBD cells cultured in vitro indicating clear phenotypic differences between the two cell populations. Microarray analyses of expanded cultures confirmed that both cell types have unique transcriptional profiles with predicted functional differences in lipid, carbohydrate, nucleic acid and drug metabolism. In conclusion, we have isolated a distinct clonogenic population of epithelial cells from primary human fetal gallbladder with stem cell characteristics and found it to be unique compared to IHBD cells. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Stem Cell Research 02/2015; 18(3). DOI:10.1016/j.scr.2014.12.003 · 3.69 Impact Factor
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    • "Based on in vitro studies, ultrastructural analyses, and cell transplantation assays, ADCs have been proposed to function as bipotent facultative stem cells, giving rise to both hepatocytes and BECs, during toxin-mediated liver injury, although this issue is controversial (Españ ol-Suñ er et al., 2012; Fausto and Campbell , 2003; Friedman and Kaestner, 2011; Furuyama et al., 2011; Huch et al., 2013; Malato et al., 2011; Zaret and Grompe, 2008). Furthermore, adult hepatocytes exhibit significant plasticity in vivo, a phenomenon that may give the appearance of stem-cell-mediated differentiation (Michalopoulos et al., 2005; Tanimizu et al., 2014; Yanger et al., 2013). "
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    ABSTRACT: The liver is thought to utilize facultative stem cells, also known as "oval cells" or "atypical ductal cells" (ADCs), for regeneration following various types of injury. However, this notion has been based largely on in vitro studies and transplantation models; where lineage tracing has been used, results have been conflicting and effect sizes have been small. Here, we used genetic and nucleoside analog-based tools to mark and track the origin and contribution of various cell populations to liver regeneration in vivo following several ADC-inducing insults. We report that, contrary to prevailing stem-cell-based models of regeneration, virtually all new hepatocytes come from preexisting hepatocytes.
    Cell Stem Cell 08/2014; 15(3). DOI:10.1016/j.stem.2014.06.003 · 22.27 Impact Factor
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