Nuclear Myosin 1 regulates platelet activation and immune response in mice

Abstract

Cellular differentiation involves a complex series of events associated with change 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 on maintaining 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. In the present study, we explored the role of NM1 during differentiation of hematopoietic progenitor stem cells to terminal blood and bone marrow stromal cells. Remarkably, we found that NM1 deletion leads to differential expression of genes associated with platelet activation, immune system response and osteoclast differentiation with glycolysis-dependent processes being upregulated while oxidative phosphorylation-dependent processes being generally suppressed in bone marrow tissue isolated from NM1 knock-out mice. The study provides novel insights into the underlying mechanisms of hematopoietic differentiation and suggests that NM1 is a potential therapeutic target for blood-related disorders.