From teratocarcinomas to embryonic stem cells

Abstract

The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so-called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem-cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential.

Cdx2Efficiently Induces Trophoblast Stem-Like Cells in Naïve, but Not Primed, Pluripotent Stem Cells

“…To determine whether other pluripotent stem cell lines differ in developmental potential, we next asked whether ECCs could give rise to TSCs. ECCs can contribute to fetal development in chimeras [38][39][40][41], suggesting that ECCs and ESCs are comparable in terms of developmental potential. To determine whether ECCs can also give rise to TSCs following Cdx2 overexpression, we introduced the Cdx2ER expression plasmid, selected subclones expressing appropriate levels of Cdx2ER ( Supplementary Fig.…”

Self-renewal of teratocarcinoma and embryonic stem cells

“…Here, we simply summarize a few points about these tumours; for fuller discussions, the reader is referred to some excellent reviews (Stevens, 1983;Andrews, 2002). In pioneering work carried out from the mid-1950s, Stevens demonstrated that teratomas arise spontaneously in the testes of B1% of mice of strain 129.…”

Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress

“…Embryonic stem cells (ESCs) are derived from the inner cell mass of the early embryo, at the blastocyst stage [1], but can be maintained indefinitely in a pluripotent state in culture under appropriate conditions [2]. The embryonic cells to which they correspond give rise to lineages leading to all the somatic cells of the developing embryo, so that any defects that occur in their genome or epigenome at this early-stage would have devastating consequences for the embryo as a whole.…”