Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance

Table 1

Models of gliomagenesis. Summary of genetically engineered murine models and lentiviral systems which are targeted specific CNS cell types to reproduce the genetic alterations of GBM, the gliomagenic process, and to detect the tumor cell of origin.

Model types and mutations in targeted CNS cells	Cell of origin of glioma
Holland et al., 2000 [21]; Ras/Akt mutations in neural progenitors (Nestin^+) and in differentiated astrocytes (GFAP+)	Nestin expressing cells: NSCs and progenitor cells
Alcantara Llaguno et al., 2009 [22]; p53, PTEN, and NF1 knockout mice	Nestin expressing cells: NSCs or progenitor cells in SVZ
Wang et al., 2009 [23]; Mutated p53 model	Nestin/oligo2-positive cell population
Lindberg et al., 2009 [24]; Liu et al., 2011 [25]; P53 and NF1 knockout mice	OPCs
Koso et al., 2012 [26]; A transposon-mediated mutagenesis; Approach in isolated mouse NSCs	Astroglia mutagenized; NSCs most sensitive to oncogenic transformation after differentiation to the astrogial lineage
Dai et al., 2001 [27]; PDGFR activation via RCAS-tVA	Neural progenitors in the SVZ
Marumoto et al., 2009 [28]; Lentiviral delivery of Kras/Akt oncogenes	Neural progenitors in the SVZ
Zheng et al., 2008 [29]; Jacques et al., 2010 [30]; PTEN/p53 inactivation	Neural progenitors in the SVZ
Bachoo et al., 2002 [31]; Ink4a-ARF knockout	NSCs and astrocytes
Bruggeman et al., 2007 [32]; Bmi knockout	NSCs and astrocytes
Uhrbom et al., 2002, 2005 [33, 34]; Combined Ink4a-ARF knockout and Kras activation	Neural progenitors and astrocytes

NCSs: neural stem cells, OPCs: oligodendrocyte progenitor cells (modified from Modrek et al., 2014 [38]).