Embyronic stem cell differentiation

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Appropriate control of cellular differentiation is critical for coordinating growth and patterning during embryonic development and is essential for maintaining the health and reproductive fitness of adult organisms. Differences in the onset and extent of cellular differentiation underlie much of what is manifest as phenotypic variation in natural populations. However, when the processes are severely deregulated or disrupted they can lead to disease and compromise viability. Cellular differentiation is therefore an area of fundamental importance in biological research and improved understanding of the underlying processes has many beneficial applications in biotechnology, agriculture and biomedicine. All differentiated cells in a mammalian embryo originate from a cluster of unspecialised cells within the inner cell mass of the blastocyst. When these founder cells are explanted in culture they can give rise to pluriptotent embryonic stem (ES) cell lines that will proliferate indefinitely and retain the capacity to differentiate into all embryonic cell types. At present, ES cell lines are routinely derived from blastocysts of mice and a limited number of primates, including human, and represent a unique resource for investigating the basic molecular mechanisms that control differentiation. The ability of ES cells to differentiate into germ cells and reprogramme efficiently upon nuclear transfer also makes them an important tools for genetic modification. Efficient proliferation of undifferentiated ES cells in vitro requires continual suppression of differentiation by extrinsic factors. Disruption of prodifferentiative signaling pathways by mutation or pharmacological inhibition enhances ES cell self-renewal and reduces dependence on extrinsic factors. It seems therefore that tight regulation of prodifferentiative signals is critical for maintaining ES cell pluripotency and self-renewal, as well as driving acquisition of the differentiated phenotype.

unavailable