Somatic stem cells require a tight balance between proliferation and quiescence to ensure life-long replenishment of tissues. A disturbance in this balance can have severe consequences. The role of metabolism in this process has only recently gained attention and remains poorly understood. A better knowledge of metabolic stem cell regulation may offer new avenues to control stem cell behavior and may have important clinical implications.

The main focus of the Laboratory of Stem Cell Metabolism are adult neural stem cells (NSPCs), which give rise to new neurons throughout adulthood. This process is called adult neurogenesis and has been shown to be disturbed in various cognitive diseases. We are interested in the metabolic regulation of neurogenesis in health, aging and disease, covering basic aspects of metabolic regulation as well as extrinsic influences on NSPC metabolism.

Furthermore, we are exploring whether there are common mechanism of metabolic regulation in different somatic stem cell compartments.

We are using innovative techniques such as CRISPR/Cas9 mediated genetic modifications, various transgenic mouse models, virus-mediated gene expression in vitro and in vivo, time-lapse imaging, mass spectrometry imaging as well as proteomic, metabolomic and lipidomic approaches to address the following main topics:

i) Basic biology of lipid metabolism in NSPCs

We have previously shown that lipid metabolism is indeed crucial for NSPC behavior (Knobloch et al. Nature 2013, Knobloch et al. 2017, in revision). However, why these lipids are so important for NSPCs and how they exert their influence on NSPC behavior remains poorly understood. We will address how lipid metabolism changes during cell cycle, fate choice and differentiation, and what the lipids are used for.

ii) Extrinsic influences on metabolism in NSPCs

Many extrinsic factors are known to influence neurogenesis, such as for instance nutrition, physical activity, aging and various diseases. However, how this pro-and anti-neurogenic stimuli are translated into changed NSPC behavior remains unclear. We will address how NSPC metabolism changes upon these different stimuli.

iii) Common mechanisms of metabolic regulation in different somatic stem cell compartments

It is highly likely that different somatic stem cells share similar mechanisms of metabolic regulation. However, this possibility has not been addressed in depth. We will compare metabolic processes in different somatic stem cells, focusing on lipid metabolism, to determine the degree of conserved stem cell control mechanisms.

Keywords

• Neural stem cells
• Somatic stem cells
• Metabolism
• Lipids
• Cell fate
• Nutrition
• Health
• Aging