Abstract
Adult stem cells constitute an important reservoir of self-renewing progenitor cells and are crucial for maintaining tissue and organ homeostasis. The capacity of stem cells to self-renew or differentiate can be attributed to distinct metabolic states, and it is now becoming apparent that metabolism plays instructive roles in stem cell fate decisions. Lipids are an extremely vast class of biomolecules, with essential roles in energy homeostasis, membrane structure and signaling. Imbalances in lipid homeostasis can result in lipotoxicity, cell death and diseases, such as cardiovascular disease, insulin resistance and diabetes, autoimmune disorders and cancer. Therefore, understanding how lipid metabolism affects stem cell behavior offers promising perspectives for the development of novel approaches to control stem cell behavior either in vitro or in patients, by modulating lipid metabolic pathways pharmacologically or through diet. In this review, we will first address how recent progress in lipidomics has created new opportunities to uncover stem-cell specific lipidomes. In addition, genetic and/or pharmacological modulation of lipid metabolism have shown the involvement of specific pathways, such as fatty acid oxidation (FAO), in regulating adult stem cell behavior. We will describe and compare findings obtained in multiple stem cell models in order to provide an assessment on whether unique lipid metabolic pathways may commonly regulate stem cell behavior. We will then review characterized and potential molecular mechanisms through which lipids can affect stem cell-specific properties, including self-renewal, differentiation potential or interaction with the niche. Finally, we aim to summarize the current knowledge of how alterations in lipid homeostasis that occur as a consequence of changes in diet, aging or disease can impact stem cells and, consequently, tissue homeostasis and repair.
Highlights
Adult stem cells, referred to as “tissue” stem cells, are relatively undifferentiated cells that have the ability to self-renew and produce differentiating progeny
Studies in Pluripotent stem cell (PSC) and Mesenchymal stem cell (MSC) suggest that stem cells may generally contain lipids with a higher degree of unsaturation, when compared to differentiating progeny
What is clear is that fatty acid oxidation (FAO) and lipid biogenesis pathways appear to be common regulators of adult stem cell behavior
Summary
Referred to as “tissue” stem cells, are relatively undifferentiated cells that have the ability to self-renew and produce differentiating progeny. They are crucial for maintaining tissues that must be constantly replaced and serve as a reservoir of cells that can be used to repair damaged tissues after wounding or exposure to environmental insults. The capacity of stem cells to self-renew or differentiate can be attributed to distinct metabolic states and it is becoming apparent that metabolism plays instructive roles in stem cell fate decisions (Ito and Suda, 2014; Chandel et al, 2016; Folmes and Terzic, 2016; Mana et al, 2017; Shyh-Chang and Ng, 2017). An increased appreciation of the involvement of lipids in metabolic diseases such as obesity, atherosclerosis, stroke, hypertension, diabetes and cancers (Wymann and Schneiter, 2008), together with technological advances in mass spectrometry and computational methods and global efforts like the LIPID MAPS (Metabolites And Pathways Strategy) consortium (Fahy et al, 2005), have pushed lipid biology to the forefront of metabolism research
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