Regulation of Apoptosis and Differentiation by p53 in Human ...

CHAPTER 1: Introduction
The mouse embryonic stem cells (mESC) were the first mammalian ESC derived and this was
achieved by Evans, Kaufman and Martin in 1981 (Evans and Kaufman, 1981; Martin, 1981).
Therefore, most of our understanding of the molecular mechanisms governing self-renewal of
ESC, and requirements for growth and lineage commitment in the early mammalian embryo, are
based on the mouse model. However, extensive studies on both mouse and human ESC have
shown substantial differences, such as the dependence of mESC on leukemia inhibitory factor
(LIF) to maintain their undifferentiated state (described latter in this chapter), and this may be
explained by significant divergence between mouse and human development and/or to the fact
that these cells are isolated/derived at different time points of development (Pera and Trounson,
2004).
1.1.1- Criteria to define an embryonic stem cell
According to Pera et al (Pera et al., 2000) and considering mESC as standard, there are several
criteria that can be used to define an ESC: 1) it originates from a pluripotent cell population, 2) it
is stably diploid and karyotypically normal in vitro, 3) it can be cultured indefinitely in its primitive
state, 4) it can differentiate into tissues of the three embryonic germ layers: endoderm, mesoderm
and ectoderm in vitro or teratomas and 5) it can give rise to any cell in the body when injected
into a host blastocyst. All these criteria have been confirmed by experimentation for mESC and
mouse embryonic germ cells. Due to ethical reasons, it is not possible to validate the last criterion
in hESC (Pera et al., 2000).
1.1.2- Stem cell markers
Pluripotent cells are characterized by distinctive cellular markers and properties that relate to their
uncommitted state. These markers were first identified in hECC and in the early embryo and are
particularly useful to follow stem cell populations and for isolation purposes.
In order to characterize hESC a number of cell surface markers are currently used, including
glycolipids and glycoproteins, such as SSEA3, SSEA4, Tra-1-60, Tra-1-81, GCTM2 and CD9.
Despite their identification, the function of most of these markers is not completely understood.
CD9 is a tetraspanin transmembrane protein and has probably a role in the organization of
integrins and other receptors at the cell surface and has been implicated in mESC maintenance
(Oka et al., 2002) and its expression is induced by STAT3 activation.
Some common ESC surface markers and their presence in both human and mouse cells are
shown in table 1.1.
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