Transposable element dynamics in glioblastoma stem cells: insights from locus-specific quantification

Area of Science:

• Genomics
• Cancer Biology
• Neuro-Oncology

Background:

• Glioblastoma (GBM) has poor prognosis, driven by glioblastoma stem cells (GSCs).
• Transposable elements (TEs) are upregulated in GSCs, influencing gene expression and genomic instability.

Purpose of the Study:

• To investigate TE expression profiles in GSCs to identify distinct subpopulations.
• To explore the regulatory roles of TEs in GSC gene expression.

Main Methods:

• Analysis of bulk RNA sequencing data from 42 GSCs.
• Utilized `telescope` for locus-specific TE quantification.
• Applied consensus clustering to identify GSC subpopulations based on TE expression.

Main Results:

• Identified 858 expressed TE loci, defining two GSC clusters with differential TF and gene expression.
• One cluster showed a mesenchymal signature, with SOX11 motif enrichment in LINE elements.
• Under-expression of SOX11 correlated with decreased LINE expression in the mesenchymal GSC cluster.

Conclusions:

• TEs may play a regulatory role in GSC transcription.
• TEs influence gene expression landscapes in GSCs, potentially impacting glioblastoma recurrence.
• Further investigation into TE regulatory roles could yield therapeutic implications for glioblastoma.