Hemopoietic lineage commitment decisions:: in vivo evidence from a transgenic mouse model harboring μLCR-βpro-LacZ as a transgene

A substantial body of published data suggests activation of lineage-specific genes in multipotential hemopoietic cells before their unilineage commitment. Because the behavior and plasticity of cells isolated in vitro away from microenvironmental constraints exercised in vivo may he altered, one wonders whether similar findings can be observed in a physiologic setting in vivo. We used a transgenic mouse model harboring human micro LCR together with beta promoter sequences as a transgene to examine activation of lineage-specific programs in vivo. By using LacZ as a reporter, we had the ability to detect, quantitate, and select live cells with different levels of LacZ activation. We found strong expression of LacZ by X-gal staining in 2 lineages-erythroid and megakaryocytic. Activation in the latter was a never finding not previously observed when similar transgenes were used. We also found activation of mu LCR-beta pro at low levers in progenitor cells of granulocytic-macrophagic, erythroid, or megakaryocytic lineage detected by in vitro assays, suggesting activation before commitment to a specific lineage pathway. in particular, the expression of LacZ was graded among progenitors, so that in a proportion of them activation occurred only after commitment to erythroid or megakaryocytic lineage, In addition, we found quantitative reduction in LacZ expression between fetal river and bone marrow-derived cells, the basis of which is unclear. Collectively our data provide in vivo evidence supporting the view that lineage-specific genes are expressed in a graded fashion in pluripotential cells before their irreversible unilineage commitment. (C) 2000 by The American Society of Hematology.