Phenotypic diversity of @entity1 -derived XXXX populations in stem cell medium.

@entity1 @entity3060 @entity5 @entity15156 @entity519 @entity320
UNASSIGNED: @entity320 are highly heterogeneous @entity5 and there is no treatment effective at achieving long-term remission for @entity320 @entity1 . Thus, an appropriate model system for studying @entity320 biology and response to drugs is necessary. It has been shown that composition of the medium is a critical factor in preserving the complexity of the @entity5 in in vitro settings, and melanospheres maintained in stem cell medium are a good model in this respect. In the present study, we observed that not all @entity320 @entity1 -derived cell populations grown in stem cell medium were capable of forming melanospheres, and cell aggregates and anchorage-independent single-cell cultures emerged instead. Self-renewing capacity and unlimited growth potential indicated the presence of cells with stem-like properties in all @entity1 -derived populations but immunophenotype and @entity3060 expression exhibited variability. Enhanced @entity3060 expression and activity was observed in melanospheres in comparison with cell aggregates and single-cell culture, and @entity519 -like conditions that increased the ability of single-cell population to form melanospheres enhanced @entity3060 expression and cell pigmentation as well. Thus, @entity3060 seems to be a critical transcription factor for formation of both @entity1 -derived and @entity519 -induced melanospheres. After 2 years of continuous culturing, melanospheres progressively underwent transition into cell aggregates that was accompanied by changes in expression of several @entity3060 -dependent genes associated with melanogenesis and survival and alterations in the composition of subpopulations but not in the frequency of @entity15156 -positive cells. Several biological properties of parent @entity5 are well preserved in @entity1 -derived melanospheres, but during prolonged culturing the heterogeneity is substantially lost when the melanospheres are substituted by cell aggregates. This should be considered when cell aggregates instead of melanospheres are used in the study of @entity320 biology and cell response to drugs.Laboratory Investigation advance online publication, 13 April 2015; doi:10.1038/labinvest.2015.48.
