BMC seminar - Redox Regulation of Stem Cell Fate During Development

BMC seminar Thursday 13 November at 12:30-13:10 in Árnagarður, room 306

Speaker: Dr. Agnes Ulfig post-doc at Hans Tómas Björnsson lab, Faculty of Medicine, University of Iceland

Title: Redox Regulation of Stem Cell Fate During Development

Abstract: Pluripotent embryonic stem cells (ESCs) can develop into any cell type in the body. Yet, the regulatory mechanisms that govern cell fate decisions during embryogenesis remain largely unknown. I now demonstrate that mouse ESCs (mESCs) display large natural variations in mitochondrial reactive oxygen species (mitoROS) levels that individualize their nuclear redox state, H3K4me3 landscape and cell fate. While mESCs with high mitoROS levels (mitoROSHIGH) differentiate towards mesendoderm and form the primitive streak during gastrulation, mESCs, which generate less ROS, choose the alternative neuroectodermal fate. Temporal studies demonstrated that ME specification of mitoROSHIGH mESCs is mediated by a Nrf2 controlled switch in the nuclear redox state, triggered by the accumulation of redox-sensitive H3K4me3 marks, and executed by a hitherto unknown ROS-dependent activation process of the Wnt signaling pathway. In summary, this study explains how ESC heterogeneity is generated and used by individual cells to decide between distinct cellular fates.

Bio: Agnes Ulfig is currently a postdoc in the laboratory of Hans Tómas Björnsson at the Faculty of Medicine, University of Iceland. She earned her Ph.D. in Biochemistry from Heinrich Heine University Düsseldorf (Germany) in 2017 and has since gained more than eight years of research experience in redox proteomics and stem cell biology. Overall, her research focuses on the role of reactive oxygen species (ROS) in health and disease, and more specifically, the redox regulation of the epigenome, developmental pathways, and protein homeostasis in stem cells under physiological and stress conditions. After finishing her biochemistry studies, she investigated the role of redox post-translational protein modifications, such as cysteine oxidation and amine chlorination, in the regulation of protein conformation and function. By developing complex in vitro co-culture models mimicking chronic inflammation, she discovered that human plasma proteins act as redox switch proteins, transforming into essential regulators of the innate immune system and protective chaperone holdases, capable of protecting other proteins against ROS-induced aggregation. After 2.5 years of postdoctoral research in Germany, Agnes received funding by postdoctoral fellowships granted from the DFG (German Research Foundation Benjamin Walter program) and Leopoldina to gain independent international research experience at the University of Michigan. There, her work focused on the role of ROS in driving cell fate decisions during early embryonic development. Now at the University of Iceland, her work centers on the neural crest and explores how oxidative stress contributes to the pathogenesis of neurocristopathies. Today, she will present her findings on how naturally differing as well as pathologically altered redox states influence the cell fate decision of individual stem cells during embryogenesis.