Epigenetics, cell cycle and stem cell metabolism. Formation of insulin-producing cells

Abstract

Stem cell (SC) differentiation requires a series of chromatin rearrangements to establish cell identity. Posttranslational modifications of histones usually regulate the dynamics of hete­rochromatin. Histones are subjected to various modifications, such as acetylation, methylation, phosphorylation and ubiquinination, and thus contribute to regulation of chromatin status and trans­criptional activity. The chemically stable pattern of methylated histones promotes cellular memory relative to external stimuli, maintaining transcription levels of adaptive genes even after elimi­nation of environmental signals. Chromatin mo­difications play an important role in the maturation of pancreatic islet cells, the establishment of a secretion pattern that stimulates the regu­lation of insulin secretion. MicroRNAs, a class of endo­genous small noncoding RNAs in eukaryotes, are important regulators of gene expression at the level of posttranscriptional mecha­nisms. MicroRNAs regulate insulin secretion, pancreatic deve­lopment, and β-cell differentiation. Pluripotent SCs are characterized by a high rate of proliferation, the ability to self-repair and the potential for differentiation in different cell types. This rapid proliferation is due to a modified cell cycle that allows cells to rapidly transition from DNA synthesis to cell division by reducing the time of gap (G1 and G2) phases. The canonical WNT/β-ca­tenin signaling pathway is characterized as a major driver of cell growth and proliferation. At G1, WNT signaling induces a transition to the S-phase. Compared to their somatic counterparts, pluripotent SCs exhibit a high rate of glycolysis similar to aerobic glycolysis in cancer cells, a phenomenon known as the Warburg effect, which is important for maintaining SC properties. In stem cells, the extracellular influx of Ca2+ into the cytoplasm is mediated mainly by depot-controlled Ca2+ channels. Extracellular cal­cium has been shown to promote SC proliferation and thus may be involved in transplant therapy.

Keywords

• stem cells
• epigenetic modifications
• cell cycle
• metabolism
• calcium ions
• insulin-producing cells