Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver

Podoplanin/gp38⁺ 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⁺ cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38⁺ cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38⁺ 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⁺ 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^–CD31^–Asgpr1^– liver cell fraction, numerous subsets could be identified that were negative for CD133 (gp38^hiCD133^–, gp38^lowCD133^–, and gp38^–CD133^–). Moreover, among the CD133⁺ cells, previously identified as progenitor population in injured liver, two subpopulations could be distinguished based on their gp38 expression (gp38^–CD133⁺ and CD133⁺gp38⁺). Importantly, the distribution of the identified subsets in inflammation illustrated injury-specific changes. Moreover, the gp38⁺CD133⁺ cells exhibited liver progenitor cell characteristics similar to the gp38^–CD133⁺ 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.

From: Eckert, C., Kim, Y. O., Julich, H., Heier, E.-C., Klein, N., Krause, E., Tschernig, T., Kornek, M., Lammert, F., Schuppan, D., Lukacs-Kornek, V. http://ajpgi.physiology.org/cgi/content/abstract/310/1/G1?rss=1