(540b) Cyclic Adenosine Monophosphate Signaling Caused Differentiation and Apoptosis in Mesenchymal Stem Cells

Stem cell has the ability to replicate itself by self-renewal and give rise to other lineage of cells by differentiation. Self-renewal requires the cell to complete the cell cycle and generate two daughter stem cells by mitosis, while differentiation is tightly coordinated with cell cycle exit. cAMP is shown to induce mesenchymal stem cells (MSCs) differentiate into neural cells, however the underlying mechanism is still unclear. In this study, we found that cAMP caused cell cycle arrest of the MSCs by down-regulating positive cell cycle regulators such as cyclin D1 and up-regulating negative cell cycle regulators like p27 and Retinoblastoma. Withdrawal from cell cycle might be directly associated with the differentiation of MSCs towards neural lineages. The characterization of neural differentiation of MSCs is generally based on morphological changes and expression of neural markers. In addition to being a cell cycle inhibitor, p27 is suggested to be involved in differentiation of many different cell types. It also plays a role in actin filament re-organization. We observed that the actin filament and microtubule bundles were re-arranged upon cAMP elevation, which occurred simultaneously with up-regulation of p27. This suggests that p27 might be involved in re-organization of the cytoskeleton and causing neuronal like morphologies, though further experiments is still underway to identify this. In addition to differentiation, co-currently apoptosis is initiated upon cAMP elevation. cAMP elevation resulted apoptosis might involve another cell cycle inhibitor p21, which is shown to play an inhibitory role in apoptosis. p21 is significantly down-regulated upon cAMP elevation and may compromise its protective role against apoptosis and lead a sub-populations of the cells towards programmed cell death.