Lipid Mediated Regulation of Adult Stem Cell Behavior

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.

Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

“…At 42 dpa, most enriched pathways are related to cell energetic metabolism, as the catabolism of branched-chain fatty acids (BCFA) and branched-chain amino acids (BCAA), suggesting an increased mitochondrial activity ( Figure 11A) (Neinast et al, 2019;Clémot et al, 2020). Active lipolysis of phospholipids and triacylglycerols, reflected in the low abundance of several BCFA species included lysoPC and lysoPE, explain the promotion of ketone body metabolism and the Krebs cycle (TCA) (Grabacka et al, 2016).…”

A bladder cancer patient-derived xenograft displays aggressive growth dynamics in vivo and in organoid culture

“…5 A,B, Tables S3 and S4). Increased lipid remodeling and cholesterol biosynthesis has been implicated in enhanced stem cell maintenance, proliferation, and tumorigenesis both in vivo and in organoids 35 , 36 . In our studies, lipid biosynthesis upregulation likely reflects the increased stem cell composition of organoids relative to stromal rich PDXs.…”

Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation

“…Lipid metabolism plays a pivotal role in stem cells physiopathology [ 108 , 109 , 110 ]. However, at the moment the number of studies about the lipidome of MSCs is limited, and mainly focused on variations in lipid composition during stem cell proliferation and differentiation [ 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ] ( Figure 2 ).…”