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Stem Cell Reports. 2017 May 9;8(5):1421-1429. doi: 10.1016/j.stemcr.2017.03.019. Epub 2017 Apr 20.

Prospective Isolation and Comparison of Human Germinal Matrix and Glioblastoma EGFR+ Populations with Stem Cell Properties.

Author information

1
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Friedman Brain Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
2
Department of Neuroscience, Friedman Brain Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
3
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4
Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Department of Pharmacological Sciences, Center for RNA Biology and Medicine and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
6
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
7
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Biozentrum, University of Basel, Basel 4056, Switzerland.
8
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Friedman Brain Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: nadejda.tsankova@mssm.edu.

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.

KEYWORDS:

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

PMID:
28434940
PMCID:
PMC5425658
DOI:
10.1016/j.stemcr.2017.03.019
[Indexed for MEDLINE]
Free PMC Article

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