Lipid Mediated Regulation of Adult Stem Cell Behavior

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.