Specific preferences in lineage choice and phenotypic plasticity of glioma stem cells under BMP4 and NOGGIN influence

GUILLERMO A. VIDELA RICHARDSON; CAROLINA P. GARCÍA; ALEJANDRO ROISMAN; IRMA SLAVUTSKY; DAMIÁN D. FERNANDEZ ESPINOSA; LEONARDO ROMORINI; SANTIAGO G. MIRIUKA; NAOMI ARAKAKI; HORACIO MARTINETTO; MARÍA E. SCASSA; GUSTAVO E. SEVLEVER

BRAIN PATHOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016 vol. 1 p. 43 - 61

1015-6305

Although BMP4-induced differentiation of glioma stem cells is well recognized, details of the cellular responses triggered by this morphogen are still poorly defined. In this study we established several glioma stem cell-enriched cell lines (GSC-ECLs) from high grade gliomas. The expansion of these cells as adherent monolayers, and not as floating neurospheres, enabled a thorough study of the phenotypic changes that occurred during their differentiation. Herein, we evaluated GSC-ECLs behavior towards differentiating conditions by depriving them of growth factors and/or by adding BMP4 at different concentrations. After analyzing cellular morphology, proliferation and lineage marker expression we determined that GSC-ECLs have distinct preferences in lineage choice, where some of them showed an astrocyte fate commitment and others a neuronal one. We found that this election seems to be dictated by the expression pattern of BMP signaling components present in each GSC-ECL. Additionally, treatment of GSCECLs with the BMP antagonist Noggin also led to evident phenotypic changes. Interestingly, under certain conditions some GSC-ECLs adopted an unexpected smooth muscle-like phenotype. As a whole, our findings illustrate the wide differentiation potential of glioma stem cells, highlighting their molecular complexity and paving a way to facilitate personalized differentiating therapies