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 language | English |
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Pages (from-to) | 1421-1429 |
Number of pages | 9 |
Journal | Stem Cell Reports |
Volume | 8 |
Issue number | 5 |
DOIs | |
State | Published - 9 May 2017 |
Keywords
- EGFR
- FACS
- RNA-seq
- germinal matrix
- glioblastoma
- glioma stem cells
- neural stem cells
- neurosphere
- transcriptome
- tumor initiation