Conversion to stem-cell state in response to microenvironmental cues is regulated by balance between epithelial and mesenchymal features in XXXX cells.

@entity146 @entity5 @entity2 @entity5962 @entity2533 @entity19099
UNASSIGNED: @entity5 cells within a @entity5 are functionally heterogeneous and specific subpopulations, defined as @entity5 initiating cells (CICs), are endowed with higher @entity5 forming potential. The CIC state, however, is not hierarchically stable and conversion of non-CICs to CICs under microenvironment signals might represent a determinant of @entity146 . How plasticity is regulated at the cellular level is however poorly understood. To identify determinants of plasticity in @entity2 we exposed eight different cell lines to @entity2533 to induce EMT and stimulate modulation of CD133(+)  CICs. We show that response to @entity2533 treatment is heterogeneous with some cells readily switching to stem cell state (1.5-2 fold CICs increase) and others being unresponsive to stimulation. This response is unrelated to original CICs content or extent of EMT engagement but is tightly dependent on balance between epithelial and mesenchymal features as measured by the ratio of expression of @entity5962 ( @entity5962 ) to @entity19099 . Epigenetic modulation of this balance can restore sensitivity of unresponsive models to microenvironmental stimuli, including those elicited by @entity5 -associated fibroblasts both in  vitro and in  vivo. In particular, @entity5 with increased prevalence of cells with features of partial EMT (hybrid epithelial/mesenchymal phenotype) are endowed with the highest plasticity and specific patterns of expression of @entity19099 and @entity5962 markers identify a subset of @entity5 with worse prognosis. In conclusion, here we describe a connection between a hybrid epithelial/mesenchymal phenotype and conversion to stem-cell state in response to external stimuli. These findings have implications for current endeavors to identify @entity5 with increased plasticity.
