Functional genomic approaches to stem cell biology
Seminar Room 1, Newton Institute
Embryonic stem (ES) cells are similar to the transient population of self-renewing cells within the inner cell mass of the preimplantation blastocyst (epiblast), capable of pluripotential differentiation to all specialised cell types comprising the adult organism. These cells undergo continuous self-renewal to produce identical daughter cells, or can develop into specialised progenitors and terminally differentiated cells. A variety of molecular pathways involved in embryonic development have been elucidated, including those influencing stem cell differentiation. As a result, we know of a number of key transcriptional regulators and signalling molecules that play essential roles in manifesting nuclear potency and self-renewal capacity of embryo-derived and tissue-specific stem cells. Despite these efforts however, a small number of components have been identified and large-scale characterisation of these processes remains incomplete. While the precise biological niche is believed to direct differentiation and development in vivo, it is now possible to utilise explanted stem cell lines as an in vitro model of cell fate assignment and differentiation. The aim of the studies discussed here is to map the global transcriptomic and proteomic activity of ES cells during various stages of differentiation and lineage commitment in tissue culture. This approach will help characterise the functional roles of key developmental regulators and yield more rational approaches to manipulating stem cell behaviour in vitro. The generation of large-scale data from microarray and functional genomic experiments will help to identify and characterise the regulatory influence of key transcription factors, signaling genes and non-coding RNAs involved in early developmental pathways, leading to a more detailed understanding of the molecular mechanisms of vertebrate embryogenesis.
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