Single-cell RNA sequencing suggests different progenitor lineages between IDH mutant and IDHwt glioma

Single-cell RNA sequencing has elucidated the heterogeneity in cancer. Single-cell glioblastoma (GBM) analyses have also proposed the resemblance of GBM cells to radial glia and outer radial glia (oRG) supporting the hypothesis that remnants of developmental tissue get reactivated in cancer. A recent study isolated neural progenitor cells (NPCs) from developing fetal human brain (gestational week 17-19) and classified NPCs based on their expression of THY1 (CD90), CD24 and EGFR. Ventricular radial glia are THY1^-CD24^-EGFR⁺ whereas oRG are THY1^-CD24^-EGFR^-. Early neuron precursors are CD24⁺THY1^-EGFR⁺ and glial progenitor cells (GPCs) are THY1⁺EGFR⁺. GPCs give rise to THY1⁺EGFR⁺PDGFRA⁺ pre-oligodendrocyte progenitor cells.

We aimed to apply the classification above to IDH mutant astrocytoma and oligodendroglioma as well as IDHwt GBM samples. We used 3 publicly available datasets: Wang (paired 74 IDHwt primary and recurrent samples), Tirosh (6 primary oligodendroglioma samples) and Venteicher (10 primary IDH mutant astrocytoma).

In IDH mutant astrocytoma, 82.67% of cells are THY1⁺. In oligodendroglioma, 80.47% of cells are THY1⁺ (mostly EGFR⁺PDGFRA⁺ in both disease entities). In IDHwt EGFR amplified primary GBM samples, 87.5% of cells are THY1^-CD24^-EGFR⁺. This percentage drops to 70.4% in the recurrent setting. THY1^-CD24^-EGFR^- cells increase from 9.7% to 23.1% at recurrence. In IDHwt EGFRwt primary GBM samples, 48.6% of cells are THY1^-CD24^-EGFR⁺ and 44.15% are THY1^-CD24^-EGFR^-. In the recurrent setting, 43.26% of cells are THY1^-CD24^-EGFR⁺ and 49.58% are THY1^-CD24^-EGFR^-.

IDH mutant gliomas and IDHwt GBM express different progenitor cell markers. THY1 is highly expressed in IDH mutant gliomas.