Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

2.2 Neural Stem Cells Introduction
and oligodendrocytes. NS cells don’t express the pluripotent specific transcrip-
tion factors Oct-4 and Nanog, but rather show expression of neural genes and
lack the expression of mesoderm and endoderm specific genes. As shown in
figure 2.3, pure NS cells can be derived from ES cells taken from the inner cell
mass (ICM) of the blastocyst or from the SVZ and germinative area of adult
and fetal brain tissue, respectively [400,403]. NS cells can be isolated from the
Figure 2.3: Sources of NS cells: (a) cultured indirectly starting from ES cells
derived from the ICM of the blastocyst; (b) cultured directly from the dissociation
of germinative areas of the fetal brain or SVZ of the adult brain. Adapted from
Pollard et al 2007 [400].
embryonic or adult mammalian brain of mice [297,427,525], primates [171] and
humans [135,145,149,436,443,512], although their precise purification remains
elusive since they cannot yet be unambiguously identified with markers. Until
recently, NS cells were mainly defined by the expression of Nestin, a cyto-
plasmic intermediate filament protein discovered by Hockfield and McKay in
1985 [195], although it is now clear that Nestin identifies neural progenitors as
well as stem cells. Nestin expression is lost in vitro with differentiation of NS
cells and, in vivo, is retained postnatally only in proliferative zones. Direct iso-
lation of NS cells from human fetal brain using flow cytometry for the cell sur-
face marker Prominin-1 (CD133) was reported by Uchida et al. in 2000 [502].
CD133 was originally shown to be a hematopoietic stem cell marker, but it is
also expressed in the SVZ of developing mice and humans on the apical mem-
brane of cells lining the lateral ventricles, with more restricted expression than
Nestin. In vitro NS cell-like cells with a marked stem cell activity have been
isolated from human fetal brain cells expressing CD133 [122]. In vivo, NS cells
have been identified as radial glial cells, expressing markers BLBP, GLAST
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