Glioma stem cell lines configured for patient-specific chemical genetic screens


Year:

Session type:

Steven Pollard1, Koichi Yoshikawa2, Ian Clarke2, Austin Smith1, Peter Dirks2

1Wellcome Trust Centre for Stem Cell Research, University of Cambridge, UK, 2The Hospital for Sick Children, University of Toronto, Canada

Abstract

Human brain tumours comprise a cellular hierarchy consistent with a stem cell foundation. Variation between gliomas may have its origin in distinct phenotypes of cancer stem cell. Derivation of stem cell lines with patient tumour-specific character would present individualised analytical, diagnostic and therapeutic opportunities. Here we demonstrate routine derivation of adherent cell lines from malignant glioma. Glioma neural stem (GNS) cells recapitulated the human disease in xenografts. However, individual GNS cell lines exhibit divergent gene expression signatures and differentiation behaviour that correspond to specific neural progenitor subtypes. The diversity of gliomas may therefore originate from distinct cancer stem cell phenotypes. GNS cell lines provide advantages over traditional neurosphere cultures for manipulation of proliferation and differentiation, clonal cell tracking and for chemical genetic screens. A pilot live cell imaging-based screen of 450 FDA-approved drugs identifies some differential sensitivities and a common susceptibility of GNS cells to perturbation of serotonin signalling.

Human brain tumours comprise a cellular hierarchy consistent with a stem cell foundation. Variation between gliomas may have its origin in distinct phenotypes of cancer stem cell. Derivation of stem cell lines with patient tumour-specific character would present individualised analytical, diagnostic and therapeutic opportunities. Here we demonstrate routine derivation of adherent cell lines from malignant glioma. Glioma neural stem (GNS) cells recapitulated the human disease in xenografts. However, individual GNS cell lines exhibit divergent gene expression signatures and differentiation behaviour that correspond to specific neural progenitor subtypes. The diversity of gliomas may therefore originate from distinct cancer stem cell phenotypes. GNS cell lines provide advantages over traditional neurosphere cultures for manipulation of proliferation and differentiation, clonal cell tracking and for chemical genetic screens. A pilot live cell imaging-based screen of 450 FDA-approved drugs identifies some differential sensitivities and a common susceptibility of GNS cells to perturbation of serotonin signalling.

Share this abstractTweet about this on TwitterPrint this pageShare on FacebookEmail this to someoneShare on LinkedIn