Biomedical Engineering Reference
In-Depth Information
Fig. 1.4 Genetic pathways regulating the formation of embryonic germ ( EG ) cells and embryonal
carcinoma ( EC ) cells from primordial germ cells. During normal development PGCs will differ-
entiate in the developing gonad and give rise to gonocytes. In vivo PGCs can also give rise to EC
cells, the stem cells of testicular germ cell tumors ( TGCT ). In mice, some of the genetic pathways
regulating that process are known and include the Te r , pgct1 , p53 , and mTR genes. In addition,
genes on chromosomes 18 and 19 and the Y chromosome can affect the incidence of TGCT.
Similarly, in vitro PGCs can give rise to another type of pluripotent stem cell, an EG cell. Some
of the growth factors that cause PGCs to turn into EG cells are also known and include FGF2, KL,
and LIF. Retinoic acid ( RA ) and Trichostatin A ( TSA ) can also affect the ability of PGCs to give
rise to EG cells, as can overexpression of the AKT kinase. Loss of the PTEN tumor suppressor
can affect the ability of PGCs to give rise to both EC and EG cells, indicating that there are at least
some shared pathways to pluripotency
studies found that TSA accelerated the process of conversion of PGCs to EG cells
possibly because TSA may make the chromatin more accessible to transcription
factors by allowing histones to become more acetylated (Durcova-Hills and Surani
2008 ). Studies on EG cell derivation provide an important insight into the mecha-
nisms regulating pluripotency and the acquisition of the stem cell state (summa-
rized in Fig. 1.4 ). The derivation of EG cells from PGCs also provides an important
experimental system with which to investigate the pathways regulating
pluripotency.
1.5
Lessons from Testicular Cancer
While studies of the molecular mechanisms guiding the formation of EG cells is a
relatively recent development, genetic studies carried out over several decades in
both mice and humans have provided some insights into the molecular mechanisms
Search WWH ::




Custom Search