Thymus cell antigen-1-expressing cells in the oval cell compartment

Mladen I. Yovchev, Jialin Zhang, David S. Neufeld, Petar N. Grozdanov, Mariana D. Dabeva

Research output: Contribution to journalArticle

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Abstract

Thymus cell antigen-1 (Thy-1)-expressing cells proliferate in the liver during oval cell (OC)-mediated liver regeneration. We characterized these cells in normal liver, in carbon tetrachloride-injured liver, and in several models of OC activation. The gene expression analyses were performed using reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR (Q-RT-PCR) of cells isolated by fluorescence-activated cell sorting (FACS), and by immunofluorescent microscopy of tissue sections and isolated cells. In normal liver, Thy-1+ cells are a heterogeneous population: those located in the periportal region do not coexpress desmin or alpha smooth muscle actin (α-SMA). The majority of Thy-1+ cells located at the lobular interface and in the parenchyma coexpress desmin but not α-SMA, i.e., they are not resident myofibroblasts. Although Thy-1+ cells proliferate moderately after carbon tetrachloride injury, in all models of OC-mediated liver regeneration they proliferate quickly and expand significantly and disappear from the liver when the OC response subsides. Activated Thy-1+ cells do not express OC genes but they express genes known to be expressed in mesenchymal stem cells (CD105, CD73, CD29), genes considered specific for activated stellate cells (desmin, collagen I-a2, Mmp2, Mmp14) and myofibroblasts (α-SMA, fibulin-2), as well as growth factors and cytokines (Hgf, Tweak, IL-1b, IL-6, IL-15) that can affect OC growth. Activated in vitro stellate cells do not express Thy-1. Subcloning of Thy-1+ cells from OC-activated livers yield Thy-1+ fibroblastic cells and a population of E-cadherin+ mesenchymal cells that gradually discontinue expression of Thy-1 and begin to express cytokeratins. However, upon transplantation these cells do not differentiate into hepatocytes or cholangiocytes. Activated Thy-1+ cells produce predominantly latent transforming growth factor beta. Conclusion: Thy-1+ cells in the OC niche are activated mesenchymal-epithelial cells that are distinct from resident stellate cells, myofibroblasts, and oval cells.

Original languageEnglish (US)
Pages (from-to)601-611
Number of pages11
JournalHepatology
Volume50
Issue number2
DOIs
StatePublished - 2009

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Thymus Gland
Antigens
Desmin
Myofibroblasts
Liver
Liver Regeneration
Carbon Tetrachloride
Reverse Transcriptase Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Yovchev, M. I., Zhang, J., Neufeld, D. S., Grozdanov, P. N., & Dabeva, M. D. (2009). Thymus cell antigen-1-expressing cells in the oval cell compartment. Hepatology, 50(2), 601-611. https://doi.org/10.1002/hep.23012

Thymus cell antigen-1-expressing cells in the oval cell compartment. / Yovchev, Mladen I.; Zhang, Jialin; Neufeld, David S.; Grozdanov, Petar N.; Dabeva, Mariana D.

In: Hepatology, Vol. 50, No. 2, 2009, p. 601-611.

Research output: Contribution to journalArticle

Yovchev, MI, Zhang, J, Neufeld, DS, Grozdanov, PN & Dabeva, MD 2009, 'Thymus cell antigen-1-expressing cells in the oval cell compartment', Hepatology, vol. 50, no. 2, pp. 601-611. https://doi.org/10.1002/hep.23012
Yovchev, Mladen I. ; Zhang, Jialin ; Neufeld, David S. ; Grozdanov, Petar N. ; Dabeva, Mariana D. / Thymus cell antigen-1-expressing cells in the oval cell compartment. In: Hepatology. 2009 ; Vol. 50, No. 2. pp. 601-611.
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abstract = "Thymus cell antigen-1 (Thy-1)-expressing cells proliferate in the liver during oval cell (OC)-mediated liver regeneration. We characterized these cells in normal liver, in carbon tetrachloride-injured liver, and in several models of OC activation. The gene expression analyses were performed using reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR (Q-RT-PCR) of cells isolated by fluorescence-activated cell sorting (FACS), and by immunofluorescent microscopy of tissue sections and isolated cells. In normal liver, Thy-1+ cells are a heterogeneous population: those located in the periportal region do not coexpress desmin or alpha smooth muscle actin (α-SMA). The majority of Thy-1+ cells located at the lobular interface and in the parenchyma coexpress desmin but not α-SMA, i.e., they are not resident myofibroblasts. Although Thy-1+ cells proliferate moderately after carbon tetrachloride injury, in all models of OC-mediated liver regeneration they proliferate quickly and expand significantly and disappear from the liver when the OC response subsides. Activated Thy-1+ cells do not express OC genes but they express genes known to be expressed in mesenchymal stem cells (CD105, CD73, CD29), genes considered specific for activated stellate cells (desmin, collagen I-a2, Mmp2, Mmp14) and myofibroblasts (α-SMA, fibulin-2), as well as growth factors and cytokines (Hgf, Tweak, IL-1b, IL-6, IL-15) that can affect OC growth. Activated in vitro stellate cells do not express Thy-1. Subcloning of Thy-1+ cells from OC-activated livers yield Thy-1+ fibroblastic cells and a population of E-cadherin+ mesenchymal cells that gradually discontinue expression of Thy-1 and begin to express cytokeratins. However, upon transplantation these cells do not differentiate into hepatocytes or cholangiocytes. Activated Thy-1+ cells produce predominantly latent transforming growth factor beta. Conclusion: Thy-1+ cells in the OC niche are activated mesenchymal-epithelial cells that are distinct from resident stellate cells, myofibroblasts, and oval cells.",
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AU - Dabeva, Mariana D.

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N2 - Thymus cell antigen-1 (Thy-1)-expressing cells proliferate in the liver during oval cell (OC)-mediated liver regeneration. We characterized these cells in normal liver, in carbon tetrachloride-injured liver, and in several models of OC activation. The gene expression analyses were performed using reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR (Q-RT-PCR) of cells isolated by fluorescence-activated cell sorting (FACS), and by immunofluorescent microscopy of tissue sections and isolated cells. In normal liver, Thy-1+ cells are a heterogeneous population: those located in the periportal region do not coexpress desmin or alpha smooth muscle actin (α-SMA). The majority of Thy-1+ cells located at the lobular interface and in the parenchyma coexpress desmin but not α-SMA, i.e., they are not resident myofibroblasts. Although Thy-1+ cells proliferate moderately after carbon tetrachloride injury, in all models of OC-mediated liver regeneration they proliferate quickly and expand significantly and disappear from the liver when the OC response subsides. Activated Thy-1+ cells do not express OC genes but they express genes known to be expressed in mesenchymal stem cells (CD105, CD73, CD29), genes considered specific for activated stellate cells (desmin, collagen I-a2, Mmp2, Mmp14) and myofibroblasts (α-SMA, fibulin-2), as well as growth factors and cytokines (Hgf, Tweak, IL-1b, IL-6, IL-15) that can affect OC growth. Activated in vitro stellate cells do not express Thy-1. Subcloning of Thy-1+ cells from OC-activated livers yield Thy-1+ fibroblastic cells and a population of E-cadherin+ mesenchymal cells that gradually discontinue expression of Thy-1 and begin to express cytokeratins. However, upon transplantation these cells do not differentiate into hepatocytes or cholangiocytes. Activated Thy-1+ cells produce predominantly latent transforming growth factor beta. Conclusion: Thy-1+ cells in the OC niche are activated mesenchymal-epithelial cells that are distinct from resident stellate cells, myofibroblasts, and oval cells.

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