Hormone Dependent Cancer

Differentiation of pluripotent embryonic stem cells, via multipotent progenitors to terminally differentiated cells, involves changes in gene expression that are tightly regulated by coordinated action of key transcription factors and epigenetic modifiers. Multipotent mesenchymal stem cells can give rise to a variety of cell types including adipocytes and skeletal myocytes. In terminally differentiated cells chromatin-modifiers serve as metabolic sensors that enable the cell to adapt to environmental cues and maintain energy homeostasis.

Our group aims at characterizing the role of lysine specific demethylase 1 (Lsd1) in fate determination and differentiation of mesenchymal stem cells as well as in metabolic processes of mature adipose tissue and skeletal muscle cells. Generation of mouse models with somatic-targeted mutations allows us to unravel the influence of Lsd1 on the homeostasis of metabolic organs. In addition, we established cell culture models based on preadipocyte and myoblast primary cultures to corroborate in vivo experiments.

Genome-wide binding, transcriptome, and mass spectrometry analyses allow us to unravel the molecular network through which Lsd1 governs cell differentiation and maintenance of metabolic capabilities. Understanding molecular mechanisms through which epigenetic modifiers mesenchymal stem cell differentiation and homeostasis offers new therapeutic perspectives for human metabolic disorders.  

Literature

Duteil D., Tosic M., Schüle R. (2017). Lsd1, a metabolic sensor of environment requirements that prevents adipose tissue from aging. Adipocyte 26:1-6. doi: 10.1080/21623945.2017.1345831.

Duteil, D., Tosic, M., Willmann, D., Georgiadi, A., Kanouni, T. and Schüle, R. (2017). Lsd1 prevents age-programed loss of beige adipocytes. PNAS 114(20):5265-5270.

Duteil, D., Tosic, M., Lausecker, F., L, Nenseth, H. Z., Müller, J. M., Urban, S., Willmann, D., Petroll, K., Messaddeq, N., Arrigoni, L., Manke, T., Kornfeld, J.-W., Brüning, J.C., Zagoriy, V., Meret, M., Dengjel, J., Kanouni, T. and Schüle, R. (2016). Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue.  Cell Reports 17: 1008–1021.

Duteil D., Metzger E., Willmann D., Karagianni P., Friedrichs N., Greschik H., Günther T., Buettner R., Talianidis I., Metzger D., Schüle R. (2014). LSD1 promotes oxidative metabolism of white adipose tissue Nat. Commun. 5:4093.

• Press release 2017
• Press release 2016
• Press release 2014