Wnt signaling regulates hemopoiesis through stromal cells.
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.
Yamane
T
T
Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-machi, Yonago 683-8503, Japan. yamanet@grape.med.tottori-u.ac.jp
Kunisada
T
T
Tsukamoto
H
H
Yamazaki
H
H
Niwa
H
H
Takada
S
S
Hayashi
S I
SI
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005260:Female; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D007739:L Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology*; D013753:Tetracycline Resistance / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014162:Transfection; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D011506:Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin