[Differentiation of hepatic and hematopoietic stem cells: study of liver regulation protein (LRP)].
In the adult liver, the plasma membrane Liver Regulating Protein (LRP) has been found to participate in the recognition signals between hepatocytes and rat liver epithelial cells (RLECs) and to play a critical role in the functional stability of hepatocytes. Here, we report the involvement of LRP in hematopoiesis. First, LRP was evidenced in the hematopoietic fetal rat liver and in adult rat bone marrow. Then, the involvement of LRP in adult rat and human hematopoiesis was investigated in coculture of hematopoietic cells with RLECs. In the rat, RLECs sustain long-term production of hematopoietic cells and committed progenitors as well as bone marrow stroma cells. These effects can be specifically blocked by addition of anti-LRP antibodies to both culture systems. The supportive activity of RLECs on human hematopoiesis was assessed by comparison to the reference MS-5 cell line from both unifractioned and purified CD34(+)CD38(-) hematopoietic cells. Taken together, our results argue for the involvement of LRP in heterotypic interaction signals mediated by RLEC and bone marrow stromal cells which lead to hematopoietic primitive progenitors development. They might lead to interesting applications in fundamental research, pharmacology and therapeutics.
INSERM U 49, Unité de Recherches Hépatologiques, Hôpital Pontchaillou, F-35033 Rennes Cedex, France.
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Lamy
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Corlu
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Guguen-Guillouzo
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D005333:Fetus; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008099:Liver / Q000166:cytology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051381:Rats; D011971:Receptors, Immunologic / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic