Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.1 The Cancer Stem Cell Hypothesis Introduction
Figure 3.2: (a) Asymmetric cell division, in which each stem cell (orange) generates
one daughter stem cell and one daughter destined to differentiate (green). (b-c)
Population strategies that provide dynamic control over the balance between stem
cells and differentiated cells, a capacity that is necessary for repair after injury or
disease. In this scheme, stem cells are defined by their "potential" to generate both
stem cells and differentiated daughters, rather than their actual production of a
stem cell and a differentiated cell at each division. (b) Symmetric cell division: each
stem cell can divide symmetrically to generate either two daughter stem cells or two
differentiated cells. (c) Combination of cell divisions: each stem cell can divide either
symmetrically or asymmetrically. Adapted from Morrison et al 2006 [345].
that non-stem cells cannot effectively initiate cancers, a concept that contrasts
with the commonly held idea that cancers may arise from any tissue cell with
equal likelihood [420]. Although adult stem cells are attractive candidates to
fulfill the role of tumour-initiating cells, two of their properties are also con-
sidered limitations to that end: firstly, asymmetric division potentially limits
the number of stem cells and therefore the incidence with which they could
drive tumourigenesis, and secondly, the immortal DNA strand co-segregation 35
process reduces the rate at which they can accumulate mutations. Through
the DNA strand co-segregation molecular manoeuvre, adult stem cells reduce
their mutation rate by more than 1000-fold, avoiding all mutations that arise
from replication errors that are not properly repaired [420].
Since all stem cells alike must self-renew and regulate the relative balance be-
tween self-renewal and differentiation, and cancer can be considered a disease
of unregulated self-renewal, understanding the regulation of normal stem cell
self-renewal is fundamental to understanding the regulation of cancer cell pro-
liferation [458]. By maintaining at least some of the properties of their tissue
35 Non random segregation of the set of chromosomes with the oldest template of the DNA
strands operated at each cell division.
59