DKFZ Junior Group Metabolism and Stem Cell Plasticity
Dr. Alexandros Vegiopoulos
The work of the Vegiopoulos lab aims at understanding the control of stem cell function by organismal metabolism. We focus on adipose tissue mesenchymal stem/stromal cells (MSCs) - immature cells partly associated with the vasculature - which contribute to tissue remodelling by adopting different fates incl. the formation of new adipocytes. In particular, we are interested in the role of MSCs in nutrition-driven early adipose tissue growth, leading to childhood obesity and the programming of adult metabolic disease. In addition, we are exploring the regulation of the oxidative brown adipocyte fate of MSCs, which is triggered by organismal cold exposure and conveys protection from metabolic disease.
The mechanisms relaying systemic metabolic states into MSC responses as well as the regulation of plasticity of these cells are far from being understood. Our goal has been to dissect the metabolic and signalling networks driving MSC responses, in particular cell activation and proliferation, as well as programming of differentiation. In this direction we have recently demonstrated a key signalling role of prostaglandins in the activation of adipose tissue MSCs and the induction of lipid-burning brown adipocytes.
The direction of our research is driven by three specific objectives.
- To understand how the microenvironment relays systemic metabolic states to control MSC proliferation and adipose tissue expansion in early-onset obesity.
- To define the long-term consequences of young-age MSC responses for body weight regulation and chronic disease risk.
- To identify signalling pathways controlling MSC fate, in particular the differentiation towards white versus beneficial oxidative adipocytes.
Our approach is based on 3 pillars: (A) mouse models for environmental metabolic challenges, including nutritional manipulation, (B) primary MSC culture systems, enabling molecular investigation under niche-like conditions, and (C) patient-specific human adipose tissue MSCs. In combination with the manipulation of target pathways this approach enables us to investigate the molecular mechanisms linking organismal metabolism to MSC function. Through our cooperation with the Institute of Diabetes and Cancer at the Helmholtz Center Munich we have access to state-of-the-art technology and expertise in the field of metabolism.
With our work we envisage to reach conclusions relevant to the prevention and management of childhood obesity as well as its relation to adult metabolic disease. Finally, given that obesity increases the risk of cancer, we expect to contribute to the elucidation of common mechanistic links between organismal metabolism and normal versus neoplastic tissue growth.
Bayindir, I., Babaeikelishomi, R., Kocanova, S., Sousa, I.S., Lerch, S., Hardt, O., Wild, S., Bosio, A., Bystricky, K., Herzig, S., & Vegiopoulos, A. (2015). Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning. Frontiers in Endocrinology (Lausanne) 6, 129
Vegiopoulos, A., Müller-Decker, K., Strzoda, D., Schmitt, I., Chichelnitskiy, E., Ostertag, A., Berriel Diaz, M., Rozman, J., Hrabe de Angelis, M., Nüsing, R.M., Meyer, C.W., Wahli, W., Klingenspor, M., & Herzig, S. (2010). Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science, 328(5982), 1158-61
Herzig, S. & Vegiopoulos, A. (2012). Obesity, Diabetes and Cancer. Adipositas, 6, 48-51
Berriel Díaz, M., Herzig, S., & Vegiopoulos, A. (2014). Thermogenic adipocytes: From cells to physiology and medicine. Metabolism, 63(10), 1238-49