About this Research Topic
Nutrient sensing is a fundamental process all cells use to integrate environmental signals into appropriate cellular responses. Disruptions in nutrient sensing contribute to complex diseases such as Alzheimer's disease, cancer, and diabetes. Shared mechanisms are used by cells to sense nutrients and translate nutrient flux into signaling and transcriptional changes; yet, how cells organize and control these mechanisms is poorly understood. This Research Topic seeks to illuminate how cells adapt to nutrient flux to perform essential cellular functions or in the case of cancer invade other tissue. The Research Topic is organized into 2 sections: one focusing on how stem and pluripotent cells translate nutrient flux for either self-renewal or to differentiate and second how adaptive immune cells use nutrients to drive terminal differentiation and immune response in cancer. We will be soliciting Original Research, Review, and Perspective articles for this Research Topic.
Nutrient Sensing Control of Stem Cells: Stem cells (SCs) are pluripotent (embryonic SCs) or multipotent (hematopoietic SCs, adult tissue derived-SCs from bone marrow, adipose tissue or intestinal crypts) cells having two special characteristics: a high degree of self-renewal and the capability to differentiate into different cell types. Therefore, the use of stem cells for fundamental research, translational research and therapeutic applications has soared in the last decade. Besides the potential applications of SCs benefiting disease treatment, it is now established that cancer SCs are present in heterogeneous tumors. These cells represent a sub population of cells with genetic and epigenetic alterations leading to a more aggressive and metastatic phenotype and drive chemotherapeutic resistance. For both the adult and cancer SCs, the microenvironment and cellular signals are crucial to drive SC to either proliferative or differentiation programs. Among these signals, nutrient availability and metabolic reprogramming/plasticity regulate SC behavior. Clearly, nutrient-responsive metabolites, including ATP, acetyl-CoA and UDP-GlcNAc link metabolic status with fundamental stem cell functions, by regulating stem cell-specific signaling networks and gene expression. This critical area of stem cell control will be explored in this section.
Adaptive Immunity is Regulated by Metabolites: Naïve immune cells undergo differentiation into effector immune cells. For example, CD4+ T cells differentiate into effector Th1, Th2, Th17, and Treg cells in response to immune stimulant. Th1, Th2, and Th17 cells use aerobic glycolysis during differentiation while Treg cells become more dependent on oxidative phosphorylation demonstrating the unique and different metabolic needs of these cells. Importantly, the metabolic milieu drives T cell differentiation and metabolic imbalance leads to pro-inflammatory T-cell function. For instance, impaired glutamine sensing disrupts Th17 differentiation while having little impact on Th1 function. These emerging data show the critical need to understand how nutrient flux affects immune cell function. Not only is nutrient sensing key to normal immune cell development, changes to the nutrient microenvironment of tumors have a profound effect on immune cell function and the activity of immune modulators in cancer treatment. In this section, we will gain new knowledge into how nutrient flux controls immune function, differentiation, and chronic inflammatory diseases such as cancer.
Keywords: Nutrient sensing, cancer stem cells, immunology, metabolism, metabolites
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