Description:
<jats:p> Podoplanin/gp38<jats:sup>+</jats:sup> stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38<jats:sup>+</jats:sup> cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38<jats:sup>+</jats:sup> cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38<jats:sup>+</jats:sup> cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38<jats:sup>+</jats:sup> cells significantly expanded in all three models of liver injury and returned to baseline levels during regression of inflammation. Based on CD133 and gp38 expression in the CD45<jats:sup>−</jats:sup>CD31<jats:sup>−</jats:sup>Asgpr1<jats:sup>−</jats:sup> liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38<jats:sup>hi</jats:sup>CD133<jats:sup>−</jats:sup>, gp38<jats:sup>low</jats:sup>CD133<jats:sup>−</jats:sup>, and gp38<jats:sup>−</jats:sup>CD133<jats:sup>−</jats:sup>). Moreover, among the CD133<jats:sup>+</jats:sup> cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38<jats:sup>−</jats:sup>CD133<jats:sup>+</jats:sup> and CD133<jats:sup>+</jats:sup>gp38<jats:sup>+</jats:sup>). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38<jats:sup>+</jats:sup>CD133<jats:sup>+</jats:sup> cells exhibited liver progenitor cell characteristics similar to the gp38<jats:sup>−</jats:sup>CD133<jats:sup>+</jats:sup> population, thus representing a novel subset within the classical progenitor cell niche. Additionally, these cells expressed distinct sets of inflammatory genes during liver injury. Our study illuminates a novel classification of the stromal/progenitor cell compartment in the liver and pinpoints a hitherto unrecognized injury-related alteration in progenitor subset composition in chronic liver inflammation and fibrosis. </jats:p>