Thy-1 Is Expressed in Hepatic Myofibroblasts and Not Oval Cells in Stem Cell-Mediated Liver Regeneration

Abstract

Thy-1, a marker of hematopoietic stem cells, has been reported to be expressed by oval cells proliferating during stem cell-mediated regeneration in rat liver, suggesting a relationship between the two cell populations. Consequently, Thy-1 has become an accepted cell surface marker to sort hepatic oval cells. In the present study we used the well-characterized 2-acetylaminfluorene/partial hepatectomy model to induce transit-amplification of hepatic oval cells in the regenerating liver and characterized Thy-1 expression using Northern hybridization, quantitative reverse transcriptase-polymerase chain reaction analysis, immunofluorescence confocal microscopy, and immunoelectronmicroscopy. We found that Thy-1 expression was induced during transit-amplification of the oval cell population, but Thy-1 mRNA was not present in the ␣-fetoprotein-expressing oval cells.

Portal fibroblasts marked by the surface antigen Thy1 contribute to fibrosis in mouse models of cholestatic liver injury

“…However, these histological analyses were solely performed in serial sections, which did not allow accurate evaluation of cell markers. Dezso and colleagues17 revisited Thy1 as a marker for oval cells; they performed co‐immunostaining for Thy1 and CK19, a marker for oval cells, followed by confocal microscopic analysis. As a result, no colocalization of Thy1 and CK19 was observed; instead Thy1 was later readdressed as a marker for hepatic myofibroblasts, shown by colocalization with the myofibroblast marker α‐SMA 21.…”

“…It has also been described in rats that Thy1‐expressing cells in the stem cell niche compartment behave as activated mesenchymal–epithelial cells in vitro , presumably acting as progenitor cells themselves 19, 20. On the other hand, Thy1 has been reported to be a marker of liver myofibroblasts that reside near the portal vein 17, 21, 22. These reports identify a periportal mesenchymal population of Thy1‐expressing cells that could potentially be the equivalent of PFs, which lack a definitive marker for isolation and subsequent analysis.…”

“…Thy1 is a glycosylphosphatidylinositol‐anchored cell surface protein and is widely used as a stem cell marker that is expressed in hematopoietic stem cells and mesenchymal stem cells. However, studies have revealed that Thy1 is not expressed in oval cells17, 18 but is instead a marker for cells that reside in close proximity to oval cells, constituting a “stem cell niche.”…”

Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver

“…31,32 Myofibroblasts are additionally positive for Thy-1. 12,13 In the liver, hepatic stellate cells and portal fibroblasts are able to acquire a myofibroblastic phenotype, 8,33 although it has remained difficult to distinguish myofibroblastic (activated) stellate cells from portal myofibroblasts in human liver tissue. In the current study, we showed that cells that are positive for both CYGB and CRBP-1 represent the quiescent phenotype of human stellate cells that are uniquely localized in the perisinusoidal space, and cells that are additionally positive for a-SMA are myofibroblastic (activated) human stellate cells that are predominantly present near the fibrotic septum of advanced fibrotic liver tissues.…”

“…In addition, these cells express cellular retinol-binding protein-1 (CRBP-1) and participate in the metabolism of retinol and retinyl esters. 11 In contrast, thymocyte differentiation antigen 1 (Thy-1 or CD90) [12][13][14] and fibulin-2 (FBLN2) [15][16][17] have been utilized as markers of liver myofibroblasts. These cell type-specific markers of liver fibroblastic cells have been largely utilized in studies with rodents.…”