Analytical strategies for studying stem cell metabolism

Abstract

Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology.

Metabolomics of mammalian brain reveals regional differences

“…Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectrometry are the two technologies used for metabolomics studies [22]. MS can be combined with gas and liquid chromatography (GC and LC, respectively) separation tools to better resolve the metabolites [23]. Metabolomics analyses can generally be separated into two groups: targeted and untargeted analyses.…”

Interaction Between Neurogenic Stimuli and the Gene Network Controlling the Activation of Stem Cells of the Adult Neurogenic Niches, in Physiological and Pathological Conditions

“…Overall, rescue of neurogenesis by nutrients in conditions of decreased function, such as neurodegeneration, trauma, ischemia or aging, can lead to activation of stem cells, while in physiological conditions (e.g., HTyr treatment in adult mice) nutrients appear unable to activate stem cells. This latter is somewhat surprising, if we consider that the metabolism plays a great role in the activation of stem cells (Arnold et al, 2015), as indicated by different laboratories, showing that the activation of stem cells depends on the reduction of the oxidative state (Adusumilli et al, 2019 [Preprint]) and on the activation of the metabolism of fatty acids (Knobloch et al, 2017) as well as on the inhibition of glycolysis (Llorens-Bobadilla et al, 2015) or on low density lipoprotein (LDL) downregulation (Engel et al, 2019).…”

Transgenic mouse models for studying adult neurogenesis

“…It regulates the activity of fatty acid synthase (Fasn), the key enzyme in biosynthesis of fatty acids, by reducing the availability of its substrate, malonyl-CoA. Lipid metabolism and signaling has been highly implicated in the function of stem cells, including neural stem cells (Allen and Maletic-Savatic, 2011; Allen et al, 2013; Arnold et al, 2015; Maletic-Savatic et al, 2008; Manganas et al, 2007; Walker et al, 2016). In 2013, Knobloch and colleagues showed that Fasn is highly expressed in the adult neural stem/progenitor cells of both SGZ and SVZ but downregulated after differentiation (Knobloch et al, 2013).…”