Protein arginine methyltransferase 1 in the generation of immune megakaryocytes: A perspective review

Megakaryocytes (Mks) in bone marrow are heterogeneous in terms of polyploidy. They not only produce platelets but also support the self-renewal of hematopoietic stem cells and regulate immune responses. Yet, how the diverse functions are generated from the heterogeneous Mks is not clear at the molecular level. Advances in single-cell RNA seq analysis from several studies have revealed that bone marrow Mks are heterogeneous and can be clustered into 3 to 4 subpopulations: a subgroup that is adjacent to the hematopoietic stem cells, a subgroup expressing genes for platelet biogenesis, and a subgroup expressing immune-responsive genes, the so-called immune Mks that exist in both humans and mice. Immune Mks are predominantly in the low-polyploid (≤8 N nuclei) fraction and also exist in the lung. Protein arginine methyltransferase 1 (PRMT1) expression is positively correlated with the expression of genes involved in immune response pathways and is highly expressed in immune Mks. In addition, we reported that PRMT1 promotes the generation of low-polyploid Mks. From this perspective, we highlighted the data suggesting that PRMT1 is essential for the generation of immune Mks via its substrates RUNX1, RBM15, and DUSP4 that we reported previously. Thus, we suggest that protein arginine methylation may play a critical role in the generation of proinflammatory platelet progeny from immune Mks, which may affect many immune, thrombotic, and inflammatory disorders.