Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin–SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs.
1 November 2018 in Reproductive Medicine and Biology
Background: The female reproductive tract contains an active microbiome comprising mainly bacteria from the Lactobacillus genus, which is associated with a healthy microbiome state. However, spatio‐temporal fluctuations of this microbiome that occur in response to internal and external factors may impact the physiology of the reproductive tract organs and even lead to pathological states.Methods: Current literature covering the reproductive tract microbiome is summarized and contextualized in this review.Main findings: This review presents the current knowledge about the bacterial composition of the lower and upper reproductive tract as well as the impact of the microbiota on women's health and reproduction. We place special focus on the impact of the endometrial microbiome in infertility and assisted reproductive technologies.Conclusion: The assessment of the reproductive tract microbiome adds a new microbiological perspective to human reproduction, pregnancy, and onset of new life, highlighting the importance of considering the evaluation of microbial communities to improve personalized care in reproductive medicine and women's health.