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The Journal of Immunology, 2001, 167: 765-772.
Copyright © 2001 by The American Association of Immunologists

Wnt Signaling Regulates Hemopoiesis Through Stromal Cells1

Toshiyuki Yamane2,*, Takahiro Kunisada*, Hirotake Tsukamoto*, Hidetoshi Yamazaki*, Hitoshi Niwa{dagger}, Shinji Takada{ddagger} and Shin-Ichi Hayashi*

* Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan; {dagger} Laboratory of Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe, Japan; and {ddagger} Center for Molecular and Developmental Biology, Graduate School of Science, Kyoto University, Kyoto, Japan

Hemopoietic cells develop in a complex milieu that is made up of diverse components, including stromal cells. Wnt genes, which are known to regulate the fate of the cells in a variety of tissues, are expressed in hemopoietic organs. However, their roles in hemopoiesis are not well characterized. In this study, we examined the roles of Wnt proteins in hemopoiesis using conditioned medium containing Wnt-3a. This conditioned medium dramatically reduced the production of B lineage cells and myeloid lineage cells, except for macrophages in the long-term bone marrow cultures grown on stromal cells, although the sensitivity to the conditioned medium differed, depending on the hemopoietic lineage. In contrast, the same conditioned medium did not affect the generation of B lineage or myeloid lineage cells in stromal cell-free conditions. These results suggested that Wnt proteins exert their effects through stromal cells. Indeed, these effects were mimicked by the expression of a stabilized form of {beta}-catenin in stromal cells. In this study, we demonstrated that Wnt signaling regulates hemopoiesis through stromal cells with selectivity and different degrees of the effect, depending on the hemopoietic lineage in the hemopoietic microenvironment.




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