• Guillermo Agustín Videla Richardson, Carolina Paola Garcia, Alejandro Roisman, Irma Slavutsky, Damián Darío Fernandez Espinosa, Leonardo Romorini, Santiago Gabriel Miriuka, Naomi Arakaki, Horacio Martinetto, María Elida Scassa, and Gustavo Emilio Sevlever.
• Laboratorio de Investigación aplicada a Neurociencias (LIAN), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Escobar, Provincia de Buenos Aires, Argentina.
• Brain Pathol. 2016 Jan 1; 26 (1): 43-61.

AbstractAlthough BMP4-induced differentiation of glioma stem cells (GSCs) is well recognized, details of the cellular responses triggered by this morphogen are still poorly defined. In this study, we established several GSC-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 toward 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 GSC-ECLs 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 GSCs, highlighting their molecular complexity and paving a way to facilitate personalized differentiating therapies. © 2015 International Society of Neuropathology.

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