| Embryonic stem cells, which were originally derived from the inner cell mass (ICM) of blastocyst stage mammalian embryos, have the ability to undergo self-renewal and to differentiate into any of the three primary germ layers and various cell types. The latter characteristic, pluripotency, is the basis for the idea of stem cell therapies. By harnessing the power of ES cell differentiation, researchers believe they can guide ES cells or adult stem cells to form specific mature cell types that can be used to replace damaged or dead cells in various disease states. However, to achieve the goals of stem cell therapy a more detailed understanding of stem cells and the varying mechanisms that regulate the transition of ES cells from the undifferentiated to the differentiated state are needed. We hypothesize that characterization of STAT3 function and regulation within the ES cell system may provide valuable insight into the mechanisms that control cellular differentiation.;Although many researchers have identified STAT3 as a player in ES cell pluripotency and self-renewal, this dissertation elaborates on a newly discovered function for STAT3, that being the regulation of ES cell differentiation. We present evidence suggesting that STAT3 operates in distinct signaling pathways during differentiation, depending on the ultimate cell fate. We also identify miRNAs that suppress STAT3 at the onset of ES differentiation, and our data suggest that levels of these miRNAs may affect cell fates. Combined, the data presented in this dissertation suggest that STAT3 is a master regulator of ES cell differentiation. Thus, we believe that STAT3 represents an excellent target for studies on stem cell therapeutics, as its broad role in cellular differentiation is applicable to generation of many specialized cell types. |
