Year: 2008
Type: preprint
Abstract: Stem cells are distinguished by two properties: selfrenewal and the potential to differentiate.Our understanding of the mechanisms underlying these features in vertebrate stem cells is incomplete.Whereas powerful genetic approaches in invertebrates permit delineation of the cellular components required for self-renewal and differentiation, as well as for interactions of stem cells with their niches, analogous strategies are not readily applicable to vertebrate stem cells.In considering this landscape, we chose to focus on mouse ES cells (Evans and Kaufman 1981;Martin 1981) as a tractable system in which to apply biochemical and genetic methods with the goal of providing a comprehensive description of the networks controlling self-renewal and pluripotency.Although ES cells may represent a "special case" given their origin and the artificial manner in which they are maintained in culture, they provide a convenient source of unlimited, quite homogeneous, self-renewing stem cells for biochemical studies.Moreover, the facility with which ES cells may be modified by gene-targeting or other loss-of-function approaches (e.g., si/shRNA inhibition) permits functional assessment of the contribution of specific components to the pluripotent state.Hence, in the work summarized here, our goal has been to identify in a comprehensive, relatively unbiased manner the proteins critical for maintenance of pluripotency and self-renewal and to delineate how they act individually and together in these processes.These approaches should lead to general concepts that may be applied to other stem cell systems and suggest methods for improved reprogramming of somatic cells to pluripotency (Takahashi and Yamanaka 2006;Takahashi et al. 2007) or to alternative fates.
Authors: S.H. Orkin, J. Wang, J. Kim, J. Chu, S. Rao, T.W. Theunissen, X. Shen, D.N. Levasseur
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2147441917