Nuclear Myosin 1 regulates platelet activation and immune response in mice

Cellular differentiation involves complex events associated with changes in cellular shape, function and proliferative capacity. This process is regulated by specific expression of multiple genes, which guide the cell through differentiation but also ensure proper function of terminal cell types. Over the last decade, the role of cellular metabolism in maintaining stem cells pluripotency and differentiation has been getting more attention due to a direct link between metabolic state and differentiation potential of cells. Since Nuclear Myosin 1 (NM1) deletion leads to a switch from oxidative phosphorylation to aerobic glycolysis and tumorigenesis in mice, here we asked if NM1 also contributes to cell differentiation. Indeed, analysis of metabolomic profiles and cytokine and chemokine levels upon NM1 depletion support a role in hematopoiesis. In an NM1 KO mouse model results from total blood cell count and bleeding assay show decreased erythropoiesis and thrombopoiesis as well as failure in hemostasis. Next, we explored the role of NM1 during the differentiation of hematopoietic progenitor stem cells to terminal blood cells by transcriptionally profiling bone marrow, spleen and peripheral blood from NM1 KO mice. 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. These expression patterns are preserved and become more complex in spleen and peripheral blood. The study, therefore, provides 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.