H p53 hyperphosphorylation, but not apoptosis or senescence. Next, a proteomic screen of Adenosine A3 receptor (A3R) Inhibitor medchemexpress EV-exposed HSPC identified the systematic suppression of ribosome biogenesis because the most hugely enriched Gene Ontology category. The mTOR pathway governs ribosome biogenesis and protein synthesis, and we went on to show that AML-EV trafficking of micro RNA-1246 targets Raptor, a pathway element. Translational suppression of Raptor In turn brought on ribosomal protein S6 hypo-phosphorylation and suppressed protein synthesis. Quiescent HSC are known to rely on error prone mechanisms of DNA repair, and we demonstrate that residual HSC accrue DNAOF13.Extracellular vesicles contribute towards the improvement of ionizing radiation-induced late bone marrow pathologies D id Kisa, Rita Hargitaib, Nikolett S dora, Eszter Persaa, T de Szatm ib, Enik Kisa, G a S r yb and Katalin LumniczkybaNational Public Health Center, Budapest, Hungary; bNational Public Well being Center, Division of Radiobiology and Radiohygiene, Department of Radiation Medicine, Budapest, HungaryIntroduction: Bone marrow (BM) is usually a particularly radiosensitive organ; haematological malignancies, myelodysplastic syndrome and chronic bone marrow insufficiency are viewed as long-term consequences of bone marrow irradiation. Ionizing radiation (IR) damages the stem and progenitor cells and alters signalling amongst the stem cell compartment and also the BM stroma. The main objective of our perform was to investigate extracellular vesicles (EVs) mediated IR effects in the BM and stroma at low and higher irradiation doses and to study possible underlying mechanisms employing an in vivo murine model. Solutions: C57Bl/6 mice had been irradiated with 0.1 Gy or two Gy and EVs isolated from the BM supernatant were injected systemically into naive animals. EV-mediated phenotypical modifications were determined by flow cytometry within the stem and progenitor cell compartment and in the BM stroma. Apoptosis in different cellular subpopulations was measured by Tunnel assay, DNA harm by immunostaining making use of the H2AX assay, senescence by -gal staining. Oxidative harm was evaluated in the BM cells by measuring protein oxidation and lipid peroxidation and systemically by determining the degree of 8-hydroxy-2′ -deoxyguanosine within the urine.JOURNAL OF EXTRACELLULAR VESICLESResults: Therapy of na e mice with TRPA supplier BM-derived EVs from irradiated animals induced apoptosis in certain cellular subpopulations, led to local and systemic oxidative harm, decreased the amount of haematopoietic and mesenchymal stem cells and of lymphoid progenitors, changed the ratio in between the long term and quick term stem cells, enhanced systemic release of immature progenitors in to the circulation. Stroma was less affected; endothelial cells were the most sensitive. Summary/Conclusion: BM-derived EVs mediated IRinduced damage inside the bone marrow and stroma, which raise the role of BM-derived EVs in the improvement of IR-induced late BM pathologies. Funding: Euratom research and training programme 2014018 below grant agreement No 662287 (CONCERT)OF13.Myeloid derived extracellular vesicular WNT induces rectal stem cell regeneration Payel Bhanjaa, Felipe Rodrigueza, Giselle Sanchez Guerreroa and Subhrajit SahabaResults: Histopathological analysis of Csf1r.iCre; Porcnfl/fl mice rectum demonstrated no differences in epithelial morphology compared to wild sort mice. However, exposure to PIR which depletes all RSCs demonstrated larger radio-sensitivity and considerable damage in rectum.