Open AccessSpecific Preferences in Lineage Choice and Phenotypic Plasticity of Glioma Stem Cells Under BMP4 and Noggin Influence
Author(s) -
Videla Richardson Guillermo Agustín,
Garcia Carolina Paola,
Roisman Alejandro,
Slavutsky Irma,
Fernandez Espinosa Damián Darío,
Romorini Leonardo,
Miriuka Santiago Gabriel,
Arakaki Naomi,
Martinetto Horacio,
Scassa María Elida,
Sevlever Gustavo Emilio
Publication year - 2016
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12263
Subject(s) - noggin , morphogen , phenotype , biology , neurosphere , glioma , microbiology and biotechnology , lineage markers , stem cell , lineage (genetic) , olig2 , cellular differentiation , neuroscience , cancer research , genetics , gene , bone morphogenetic protein , adult stem cell , oligodendrocyte , myelin , central nervous system
Although 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, N oggin, 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.