Nuclear myosin 1 regulates platelet activation and immune response in mice

Cellular differentiation involves a complex series of events associated with changes in cellular shape, function, and proliferative capacity. This process is mostly regulated by specific expression of multiple genes which guide the cell through the differentiation process but also ensure proper function of terminal cell types. Over the last decade, the role of cellular metabolism in maintaining the pluripotency of stem cells and subsequent differentiation is getting more attention as there is a direct link between the metabolic status of cells and their differentiation potential. We have recently shown that deletion of Nuclear Myosin 1 (NM1) leads to a molecular switch from oxidative phosphorylation to glycolysis and subsequent tumorigenesis in mice. Here we performed an in vitro analysis of metabolomic profiles associated with NM1 loss and measured the cytokine and chemokine levels in cells to provide evidence for a possible role of NM1 during hematopoiesis. Moreover, we explored the role of NM1 during the differentiation of hematopoietic progenitor stem cells to terminal blood cells by transcriptomic analysis of bone marrow, spleen, and peripheral blood. We found that in bone marrow, NM1 deletion leads to overexpression of genes associated with glycolysis-dependent platelet activation and suppression of the innate immune system genes. Remarkably, these expression patterns are preserved and become more complex in the spleen and peripheral blood. The study therefore provides novel insights into the underlying mechanisms of hematopoietic differentiation and activation of specific blood cell types and suggests NM1 as a potential therapeutic target for blood-related disorders.