In vitro, ESCs are commonly induced to differentiate via the spontaneous assembly of cell aggregates in suspension referred to as “embryoid bodies” (EBs). In recent years, an increasing emphasis has also been placed on the potent paracrine morphogenic effects of molecules synthesized and secreted by stem cells, including ESCs. The pluripotent differentiation potential of ESCs and derivation of human ESCs have also motivated the pursuit of regenerative ESC-based therapies to restore endogenous cells to tissues afflicted by traumatic injuries or chronic disease. Overall, these studies represent a novel framework to dissect the complex, dynamic nature of the extracellular biochemical milieu of stem cell microenvironments that regulate pluripotent cell fate decisions and morphogenesis.įor three decades, embryonic stem cells (ESCs) have been used as a model of mammalian developmental morphogenesis in order to define and characterize mechanisms of self-renewal and differentiation of pluripotent cells. In addition, systems analysis of ECM and growth factor gene expression alone identified intracellular molecules and signaling pathways involved in the progression of pluripotent stem cell differentiation that were not contained within the array data set. Pathway analysis generated solely from ECM and growth factor gene expression highlighted morphogenic cell processes within the embryoid bodies, such as cell growth, migration, and intercellular signaling, that are required for primitive tissue and organ developmental events. As expected, decreases in the expression of genes regulating pluripotent stem cell fate preceded subsequent increases in morphogen expression associated with differentiation. Gene expression analysis of ECM and growth factors by ESCs differentiating as embryoid bodies for up to 14 days was assessed using PCR arrays (172 unique genes total), and the results were examined using a variety of data mining methods. Thus, the objective of this study was to examine the global dynamic profiles of ECM and growth factor genes associated with early stages of pluripotent mouse embryonic stem cell (ESC) differentiation. Although temporal patterns of phenotypic gene expression have been relatively well characterized during the course of differentiation, coincident patterns of endogenous extracellular matrix (ECM) and growth factor expression that accompany pluripotent stem cell differentiation remain much less well-defined. Pluripotent stem cells are uniquely capable of differentiating into somatic cell derivatives of all three germ lineages, therefore holding tremendous promise for developmental biology studies and regenerative medicine therapies.
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