CALL FOR PAPERS - Metabolic Control of Stemness and Differentiation
Friday, 28. September 2018
Beyond energy production, recent studies have shown that metabolism and mito- chondrial biology play important roles in stem cell state and lineage speci cation. Metabolism is no longer a functional end-point of signaling events and gene regu- lation. Rather, metabolites are now understood to be active players, functioning as receptor ligands and enzyme modulators. Changes in metabolism, elicited by altered nutrient availability, as well as the distribution and quality of mitochondria, have been shown to be crucial regulators of cell fate. Consequently, the environment is a critical regulator of stem cell fate and has been shown to link nutrient availability with epigenetic changes to impact stem cell identity. Indeed, a direct link between cellular metabolism and chromatin dynamics has emerged, where metabolic intermediates of cellular metabolism act as cofactors for epigenetic modulators, thereby regulating their activity and in uencing the epigenetic landscape. Epigenetic mechanisms including modi cations of histones, incorporation of histone variants, changes in DNA methylation, ATP-dependent chromatin remodeling, and noncoding RNAs (ncRNAs) have been linked with metabolic pathway activity. e loss of pluripotency at the beginning of di erentiation is accompanied by the progressive silencing of stemness genes and the activation of subsets of cell type-speci c genes. ese processes are orchestrated by epigenetic modi cations, which can be altered and coordinated by the presence or absence of speci c metabolites. us, new global regulatory networks are emerging based on metabolism in stem cell biology.
Casting light on the regulatory mechanisms underlying the metabolic regulation of stemness and stem cell di erentiation is important not only for understanding tissue homeostasis during health and disease, but also to establish conditions which accurately support normal physiology in culture. ese studies will o er insights into the nutrient requirements of stem cells that support e cient maintenance, di erentiation, and engra ment, ensure appropriate replication of physiology in disease models, and also provide novel targets for pharmacological interventions to treat human diseases, potentially leading to new diagnostic and therapeutic steps forward in medicine. In addition, elucidating both the physiological and molecular mechanisms underlying stem cell biology and revealing the connections between cellular metabolism, mitochondria, and epigenetic regulation of stem cell division, commitment, or conversion will have important implications for advances in stem cell research and nuclear reprogramming, particularly for improving regenerative medicine approaches.
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