title: Specific Preferences in Lineage Choice and Phenotypic Plasticity of Glioma Stem Cells Under BMP4 and Noggin Influence.
abstract: 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, 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.
authors: 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.
authors: Guillermo Agustín
authors: GA
authors: Videla Richardson
authors: 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.
authors: Carolina Paola
authors: CP
authors: Garcia
authors: Laboratorio de Neuropatología, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors: Alejandro
authors: A
authors: Roisman
authors: Laboratorio de Neuropatología, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors: Irma
authors: I
authors: Slavutsky
authors: 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.
authors: Damián Darío
authors: DD
authors: Fernandez Espinosa
authors: 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.
authors: Leonardo
authors: L
authors: Romorini
authors: 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.
authors: Santiago Gabriel
authors: SG
authors: Miriuka
authors: Laboratorio de Biología Molecular, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors: Naomi
authors: N
authors: Arakaki
authors: Laboratorio de Genética de Neoplasias Linfoides, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors: Horacio
authors: H
authors: Martinetto
authors: 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.
authors: María Elida
authors: ME
authors: Scassa
authors: Laboratorio de Biología Molecular, Departamento de Neuropatología y Biología Molecular, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
authors: Gustavo Emilio
authors: GE
authors: Sevlever
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D015703:Antigens, CD; D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000099176:Noggin Protein; C525809:BMP4 protein, human
keywords: BMP4; Noggin; cancer stem cells; differentiation; glioblastoma; multipotency