The Study Of MiR-126 Function In Hematopoietic Stem Cells Of Telomere Dysfunctional Mice

MicroRNA is a non coding RNA endogenous found in eukaryotes and has a regulatory function, many reports of microRNA signaling in the hematopoietic stem cell(HSC) homeostasis and regeneration. But in telomere dysfunction in a mouse model for regulation of miRNA pathway is not relevant research work, Using the existing two gene defects in mice model(mi R-126 knock in mouse models and telomere dysfunction in mice model) to study miR-126 on HSC homeostasis maintenance and aging effect, and further to determine the miR-126 in HSC target genes. It has important scientific significance for elucidating the molecular mechanism of miR-126 in HSC senescence.Experimental results show that under normal physiological conditions of miR-126 conditional knockout mice bone marrow hematopoietic stem cell number increase, myeloid granulocyte progenitor cells number increased, the spleen hematopoietic stem cells(LSK)proportion increased, further staining detected in spleen in myeloid granulocyte ratio increased. In order to study the effects of bone marrow stem cells increased in proportion to themiR-126 gene conditional knockout mice, analyzed miR-126 gene conditional knockout mice hematopoietic stem cell cycle, the percentage of G0 phase of the miR-126 gene conditional knockout mice hematopoietic stem cells is reduced, G1, S / G2 / M ratio increased. Brdu results showed that the Brdu+ were elevated compared with the control mice. The apoptosis of hematopoietic stem cells in the whole bone marrow cells of mice was detected and the proportion of the hematopoietic stem cells in the condition of miR-126 gene knockout mice was no different with the control mice. It is proved that the increase of hematopoietic stem cells in bone marrow is due to the decrease of G0 phase and has nothing to do with apoptosis.Q-PCR check miR-126 expression of WT and G3 mice hematopoietic stem cells,The expression of miR-126 and WT in hematopoietic stem cells of G3 mice were significantly lower than that WT mice,overexpressing miR-126 in WT and G3 mice hematopoietic stem cell,after competitive bone marrow transplantation every month check peripheral blood chimerism rate showed The overexpression of miR-126 gene decreased the self-renewal ability of bone marrow stem cells in G3 and WT mice. The down-regulation of miR-126 expression in Terc-/- G3 mice is a protective mechanism for telomere dysfunction.