Specific Preferences in Lineage Choice and Phenotypic Plasticity of Glioma Stem Cells under BMP4 and Noggin Influence

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, Gustavo Emilio Sevlever

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)43-61
Number of pages19
JournalBrain Pathology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • BMP4
  • cancer stem cells
  • differentiation
  • glioblastoma
  • multipotency
  • Noggin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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