To overcome the low efficiency of gene transfer into @entity1583 cells, we developed a novel system for selective expansion of transduced cells. To this end, we constructed a chimeric cDNA (GCRER) encoding the fusion protein between the @entity24079 ( @entity24079 ) and the hormone-binding domain (HBD) of the @entity172 receptor (ER) as a selective amplifier gene. Use of the intracellular signaling pathway of @entity24079 was considered to be appropriate, because @entity24778 has the ability not only to stimulate the neutrophil production, but also to expand the @entity1583 stem/progenitor cell pool in vivo. To activate the exogenous @entity24079 signal domain selectively, the @entity172 /ER-HBD system was used as a molecular switch in this study. When the GCRER gene was expressed in the @entity3019 ( @entity3019 )-dependent @entity19 cell line, @entity19 , the cells showed @entity3019 -independent growth in response to @entity24778 or @entity172 . Moreover, the @entity19 cells transfected with the Delta(5-195)GCRER, whose product lacks the extracellular @entity24778 -binding domain, did not respond to @entity24778 , but retained the ability for @entity172 -dependent growth. Further, @entity19 bone marrow cells transduced with the GCRER or Delta(5-195)GCRER gene with retroviral vectors formed a significant number of colonies in response to @entity172 , as well as @entity24778 , whereas @entity172 did not stimulate colony formation by untransduced @entity19 bone marrow cells. It is noteworthy that erythroid colonies were apparently formed by the bone marrow cells transduced with the GCRER gene in the presence of @entity172 without the addition of @entity14190 , suggesting that the signals from the @entity24079 portion of the chimeric molecules do not preferentially induce neutrophilic differentiation, but just promote the differentiation depending on the nature of the target cells. We speculate that when the selective amplifier genes are expressed in the primitive @entity1583 stem cells, the growth signal predominates and that the population of transduced stem cells expands upon @entity172 treatment, even if some of the cells enter the differentiation pathway. The present study suggests that this strategy is applicable to the in vivo selective expansion of transduced @entity1583 stem cells.

Development of a novel selective amplifier gene for controllable expansion of transduced XXXX cells.

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen'] @entity14190 :: ('13856(Tax:10090)', 'Gene') :: ['erythropoietin'] @entity3019 :: ('16187(Tax:10090)', 'Gene') :: ['IL-3', 'interleukin-3'] @entity24778 :: ('12985(Tax:10090)', 'Gene') :: ['G-CSF'] @entity19 :: ('10090', 'Species') :: ['Ba/F3', 'murine'] @entity1583 :: ('MESH:D019337', 'Disease') :: ['hematopoietic'] @entity24079 :: ('12986(Tax:10090)', 'Gene') :: ['granulocyte colony-stimulating factor receptor', 'G-CSFR']
@entity1583 :: (MESH:D019337,Disease) :: ['hematopoietic']
