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Friday Science Review: October 7, 2011

Cell Polarity Dictated by Phosphatidylserine

Hospital for Sick Children ♦ Published in Nature Cell Biology, October 2, 2011

The enzyme Cdc42 is responsible in part for cell polarization during asymmetric cellular events. In the case of the yeast S. cerivisiae, polarization is essential during the process of budding and the formation of projections in response to mating factors. Polarization is also crucial to the operation of mammalian cells. In this Nature paper researchers show that phosphatidylserine, a type of phospholipid, is required for the correct dispersal of Cdc42 during polarization events. In an event that precedes the movement of Cdc42, phosphatidylserine is sent via secretory vesicles to the plasma membrane where it accumulates. Yeast mutants lacking phosphatidylserine synthase exhibited impairment in the polarization of Cdc42 and difficulty in budding and mating, suggesting it is at the core of regulating cellular polarization and some very important cellular processes.

Embryonic Stem Cell-Specific Splicing Event Promotes Pluripotency

University of Toronto ♦ Mount Sinai Hospital ♦ Columbia University Medical Centre ♦ Published in Cell, September 30, 2011

There are a host of genes that are upregulated in embryonic stem cells which promote stem cell-like characteristics, namely pluripotency, or the ability to give rise to all cell types in the human body. These genes include Sox2, Oct4, and Nanog, among others, and are associated with primitive cell types. Much time has been invested in researching the transcriptional networks promoting pluripotency, and how the various stem cell-specific transcription factors cross-talk with one another to ensure stem cells do not differentiate. Although these transcription factors can cross-regulate each other, on a more fundamental level they are controlled by the forkhead box (FOX) transcription factors. In this study, researchers discovered that FOX transcription factors do not always operate in the same manner. In stem cells, the FOXP1 mRNA transcript is alternatively spliced in such a manner that the FOXP1 protein has a greater affinity for the DNA promoter regions that control transcription of stem cell factors like Sox2, Oct4, and Nanog. FOXP1 also represses genes that cause differentiation. Interestingly, the FOXP1 isoform studied here could not be found in more differentiated cells, suggesting that alternative splicing is an important mechanism by which stem cells maintain their primitive status.


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