Stmc-28. intact egfr defines human germinal matrix and glioblastoma populations with shared and epigenetically imprinted stem cell properties

Epidermal growth factor receptor (EGFR) signaling is important for neural development and is frequently dysregulated in glioblastoma (GBM), but its developmental relationship to human gliomagenesis remains poorly understood. Using an EGF-ligand-binding strategy, we isolated EGFR+/– populations from fresh human germinal matrix (GM) and GBM tissues, enriching for cells with intact ligand-binding domain (EGFR+INTACT), and directly compared their downstream functional and molecular phenotypes. In both GM and GBM, only EGFR+ INTACT populations displayed stem cell properties in vitro, and in GBM, tumor initiation in vivo. Chromatin accessibility mapping revealed remarkable overlap between neoplastic and developing EGFR+ populations. Shared open chromatin regions annotated cell cycle and stemness gene sets and distinct regulatory motifs genome-wide, with footprints for ASCL1, SOX4/10, E2F1 and GABPA specifically at EGFR. Our study defines a novel population of EGFR+INTACT stem-like cells derived from fresh GM and GBM samples and implicates developmentally imprinted transcriptional regulators for their proliferation.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research