Force via integrins but not E-cadherin decreases Oct3/4 expression in embryonic stem cells

Increasing evidence suggests that mechanical factors play a critical role in fate decisions of stem cells. Recently we have demonstrated that a local force applied via Arg-Gly-Asp (RGD) peptides coated magnetic beads to mouse embryonic stem (ES) cells increases cell spreading and cell stiffness and decreases Oct3/4 (Pou5f1) gene expression. However, it is not clear whether the effects of the applied stress on these functions of ES cells can be extended to natural extracellular matrix proteins or cell–cell adhesion molecules. Here we show that a local cyclic shear force applied via fibronectin or laminin to integrin receptors increased cell spreading and stiffness, downregulated Oct3/4 gene expression, and decreased cell proliferation rate. In contrast, the same cyclic force applied via cell–cell adhesion molecule E-cadherin (Cdh1) had no effects on cell spreading, Oct3/4 gene expression, and the self-renewal of mouse ES cells, but induced significant cell stiffening. Our findings demonstrate that biological responses of ES cells to force applied via integrins are different from those to force via E-cadherin, suggesting that mechanical forces might play different roles in different force transduction pathways to shape early embryogenesis.     

A novel variant of Oct3/4 gene in mouse embryonic stem cells

OCT4 is a highly conserved gene and plays an important role during early embryonic development and differentiation. Similar to human OCT4, mouse Oct4 gene generates variants. Oct4A is a master regulator of self-renewal in pluripotent stem cells. In this study, we have identified a novel Oct4 spliced variant, designated mouse Oct4B, encoding 3 isoforms, termed Oct4B-247aa, Oct4B-190aa and Oct4B-164aa. Furthermore, we have examined the expression pattern of these isoforms in non-pluripotent cells and their function in somatic cell reprogramming. The results revealed the isoforms 247aa, 164aa localized mainly in nucleus and 190aa expressed dotted in the cytoplasm. In contrast to Oct4A, Oct4B does not function in somatic reprogramming as that of Oct4A. Taken together, our data for first time described the intact coding sequence of mouse Oct4B and its function in somatic cell reprogramming. These findings will be important for further analysis of the epigenetic mechanisms of reprogramming and highlight the necessity of discriminating Oct4 isoforms in future stem cell research.     

GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells

There is a dire need for novel therapeutics to treat the virulent malarial parasite, Plasmodium falciparum. Recently, the X-ray crystal structure of enoyl-acyl carrier protein reductase (ENR) in complex with triclosan has been determined and provides an opportunity for the rational design of novel inhibitors targeting the active site of ENR. Here, we report the discovery of several compounds by virtual screening and their experimental validation as high potency PfENR inhibitors.