ABSTRACT
Tet2 (member 2 of the Tet family) plays an important role in DNA demethylation modification, epigenetic regulation, and hematopoiesis. In our previous study, we found that Tet2 knockout mice progressively developed lymphocytic leukemia and myeloid leukemia with aging. However，the role of Tet2 in bone marrow microenvironment is unclear. Here in this study, we found that more Tet2-/- mesenchymal stem cells (MSCs) from bone marrow were in the G2/M cell cycle stages. The division time of Tet2-/- MSCs was shorter than that of the control cells. The growth rate of Tet2-/- MSCs was accelerated. The cobblestone area-forming cells assay (CAFC) showed that Tet2 knockout MSCs supported the expansion of hematopoietic stem cells (HSCs) and the differentiation of HSCs was skewed towards myeloid cells. Through the dot blotting experiment, we found that the total methylation level was increased in Tet2-/- bone marrow cells (BM). We used the methylation-chip to analyze the methylation level of Tet2-/- bone marrow cells and found that the level of methylation was increased in the transcriptional starting area (TSS), exons (EXONS) and 3' untranslated region (3' UTR). Moreover, we found that the cytokines secreted by Tet2-/- MSCs, such as IL-8 and IL-18, were decreased. While the expressions of GM-CSF and CCL-3, which supported hematopoietic stem cells to differentiate to myeloid cells, were increased in Tet2-/- MSCs. Our results demonstrated that Tet2 regulates MSCs to support hematopoiesis.
Subject(s)
Animals , Mice , Bone Marrow Cells , Cell Differentiation , DNA-Binding Proteins , Epigenesis, Genetic , Hematopoiesis , Hematopoietic Stem Cells , Mesenchymal Stem Cells , Proto-Oncogene ProteinsABSTRACT
Objective To discuss pathogenic effects of low high-density lipoprotein cholesterol(HDL-C)on atherosclerosis and thromboembolism,the influences of HDL-C on platelet cytosolic free calcium concentration([Ca2+]i),platelet release reaction products beta-thromboglobulin(?-TG)and platelet factor 4(PF4)were observed in dyslipoproteinemia patients with low HDL-C.Methods i,?-TG and PF4 were measured by fluorescent probe Fura 2-AM and ELISA skills respectively,in 42 patients with low HDLC(LHDL-C)and 25 healthy controls(CONT).Results Compared with those in CONT group,the platelet[Ca2+]i,?-TG and PF4 were all higher in LHDL-C group(all P