Loss of Tet2 affects platelet function but not coagulation in mice.

Ten-eleven translocation 2 (TET2) functions as a methylcytosine dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. TET2 has been shown to be crucial for the maintenance and differentiation of hematopoietic stem cells, and its deletion and/or mutations results in the expansion of HSPCs, and leads to hematological malignancies. mutations were found in a variety of hematological disorders such as CMML (60%), MDS (30%), MPN (13%) and AML (20%). Interestingly, it was shown that CMML patients with mutation exhibited fewer platelets than CMML patients without mutation. However, the role and function of TET2 in platelet hemostasis and thrombogenesis is not well defined. Here in this study, using a genetically engineered deletion mouse model, we found that the absence of caused a decrease in the proportion of MEP cells and hyperploid megakaryocytes. Additionally, -deficient mice displayed impaired platelet activation and aggregation under stimulation of ADP and low concentrations of thrombin, although the modestly compromised platelet function and MEP differentiation in -deficient mice could be compensated without affecting blood coagulation function. Our study indicate that deficiency leads to mild impairment of platelet function and thrombopoiesis in mice.