1. ¹Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
2. ²Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden

Correspondence: Dr L Uhrbom, Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala University, Dag Hammarsköldsväg 20, Uppsala, Uppland SE-75185, Sweden. E-mail: lene.uhrbom@genpat.uu.se

³Current address: Department of Forensic Medicine, The National Board of Forensic Medicine, Uppsala, Sweden.

Received 28 October 2008; Revised 15 February 2009; Accepted 16 March 2009; Published online 27 April 2009.

Abstract

Gliomas are primary brain tumors mainly affecting adults. The cellular origin is unknown. The recent identification of tumor-initiating cells in glioma, which share many similarities with normal neural stem cells, has suggested the cell of origin to be a transformed neural stem cell. In previous studies, using the RCAS/tv-a mouse model, platelet-derived growth factor B (PDGF-B)-induced gliomas have been generated from nestin or glial fibrillary acidic protein-expressing cells, markers of neural stem cells. To investigate if committed glial progenitor cells could be the cell of origin for glioma, we generated the Ctv-a mouse where tumor induction would be restricted to myelinating oligodendrocyte progenitor cells (OPCs) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase. We showed that PDGF-B transfer to OPCs could induce gliomas with an incidence of 33%. The majority of tumors resembled human WHO grade II oligodendroglioma based on close similarities in histopathology and expression of cellular markers. Thus, with the Ctv-a mouse we have showed that the cell of origin for glioma may be a committed glial progenitor cell.