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Background  Expression of the LIM-homeobox gene  Lhx2  in murine hematopoietic cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines. To address the molecular basis of  Lhx2  function, we generated HSC-like cell lines where  Lhx2  expression is regulated by a tet-on system and hence dependent on the presence of doxycyclin (dox). These cell lines efficiently down-regulate  Lhx2  expression upon dox withdrawal leading to a rapid differentiation into various myeloid cell types.    Results  Global gene expression of these cell lines cultured in dox was compared to different time points after dox withdrawal using microarray technology. We identified 267 differentially expressed genes. The majority of the genes overlapping with HSC-specific databases were those down-regulated after turning off  Lhx2  expression and a majority of the genes overlapping with those defined as late progenitor-specific genes were the up-regulated genes, suggesting that these cell lines represent a relevant model system for normal HSCs also at the level of global gene expression. Moreover,  in situ  hybridisations of several genes down-regulated after dox withdrawal showed overlapping expression patterns with  Lhx2  in various tissues during embryonic development.    Conclusion  Global gene expression analysis of HSC-like cell lines with inducible Lhx2 expression has identified genes putatively linked to self-renewal / differentiation of HSCs, and function of  Lhx2  in organ development and stem / progenitor cells of non-hematopoietic origin.

Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible Lhx2 expression