Studies on Cellular Regulation of Hematopoietic Microembironment

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Bone marrow provides microenvironment for self-renewal and differentiation of hematopojetic stem/progenitor cells through complex cell-cell interaction. To study the cellular regulation of hematopoietic micorenvironment, we established variety of stromal cell lines from bone marrow of temperature sensitive SV40 Large T-antigen transgenic mice and using these stromal cell lines as feeder cells, we established several stroma-dependent hematopoietic cell lines. Some stromal cell lines were shown to be mesenchymal stem cells because they can differentiate toward muscles, adipocytes, chondrocytes and smooth muscle cells in vitro and gene expression profiles of these stromal cell lines were examined by microarray analysis. We demonstrated that Oncostatin M that was produced by the hematopoietic cells regulates hematopoeiteic supporting ability and differentiation phenotypes of the stromal cells, suggesting that reciprocal cell to cell communication between stromal cells and hematopoietic cells is important to maintain the hematopoietic microenvironment.MysPDZ gene was isolated as a new gene whose expression level was correlated with the hematopoietic supportive ability of the stromal cells. MysPDZ expressed in the stromal cells contains the KE-rich and PDZ domains in the NH2-terminal, but 3 spliced isoforms (hematopoietic cell-, brain-, muscle-specific) that lack PDZ-domain in the N-terminal region are identified. Our study suggests a novel role of the KE-rich and PDZ domains in directing subcellular localization.