Abstract

Characterization of non-neoplastic and malignant human stem cell populations in their native state can provide new insights into gliomagenesis. Here we developed a purification strategy to directly isolate EGFR+/− populations from human germinal matrix (GM) and adult subventricular zone autopsy tissues, and from de novo glioblastoma (GBM) resections, enriching for cells capable of binding EGF ligand (LBEGFR+), and uniquely compared their functional and molecular properties. LBEGFR+ populations in both GM and GBM encompassed all sphere-forming cells and displayed proliferative stem cell properties in vitro. In xenografts, LBEGFR+ GBM cells showed robust tumor initiation and progression to high-grade, infiltrative gliomas. Whole-transcriptome sequencing analysis confirmed enrichment of proliferative pathways in both developing and neoplastic freshly isolated EGFR+ populations, and identified both unique and shared sets of genes. The ability to prospectively isolate stem cell populations using native ligand-binding capacity opens new doors onto understanding both normal human development and tumor cell biology.

Original languageEnglish
Pages (from-to)1421-1429
Number of pages9
JournalStem Cell Reports
Volume8
Issue number5
DOIs
StatePublished - 9 May 2017

Keywords

  • EGFR
  • FACS
  • RNA-seq
  • germinal matrix
  • glioblastoma
  • glioma stem cells
  • neural stem cells
  • neurosphere
  • transcriptome
  • tumor initiation

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