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Thursday, June 07, 2018

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Seminar: Gene regulation in the endometrium: insights on decidualization phases & hypoxia responses, Dr Kalle Rytk枚nen, Turku University
CSRL Seminar Room, Clinical Sciences Building, UHCW

Abstract: Cyclic decidualization of the uterine endometrium is crucial for human reproductive success. Decidualization is driven by differentiation of endometrial stromal fibroblasts (ESF) to decidual stromal cells (DSC). Here I will discuss two studies on the biology of DSCs: firstly, the phase specific transcriptional programs associated with decidualization, and secondly, the hypoxia responses of endometrial stromal cells. We analyzed the transcriptomes of 3-day and 8-day in vitro decidualized cells and find support for the earlier reports that decidualization occurs in at least two distinct phases. Patterns of transcription factor regulation combined with pathway analysis suggests a shift from early inflammatory signaling and protective oxidative stress signaling to a distinct late phase regulatory state.
 
Endometrium of the uterus is exposed to hypoxic periods upon menstruation as well as placentation, but transcriptomic and epigenetic regulation associated with this has not been studied. We discovered that in hypoxia both ESF and DSC up-regulate classical hypoxia response such as glycolysis pathway, but hypoxic repression of inflammatory pathways is dependent on differentiation status. We also studied oxygen dependent regulatory dynamics of the active promoter marker H3K4me3. H3K4me3 peak width has higher correlation to transcription than height, and generally broad H3K4me3 marks genes relevant for endometrial functions.

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