Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

• DOI: 10.1016/j.stemcr.2015.09.014
• Publication Date: 2015-10-25T06:32:10Z
• Authors: Helena Carén; Stefan H. Stricker; Harry Bulstrode; Sladjana Gagrica; Ewan Johnstone; Thomas E. Bartlett; Andrew Feber; Gareth Wilson; Andrew E. Teschen...; Paul Bertone; Stephan Beck; Steven M. Pollard
• Keywords: OLIG2

Glioblastoma (GBM) is an aggressive brain tumor whose growth driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany remain poorly defined. It also unclear whether arrest terminal. Here we find only a subset GSC cultures exhibit astrocyte in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they vulnerable re-entry fail appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci failed alter these were enriched SOX transcription factor-binding motifs. factors, may limit commitment. A similar propensity for de-differentiation was observed GSC-derived oligodendrocyte-like These findings highlight significant obstacles BMP-induced as therapy GBM.