Endothelial protein C receptor signaling regulates myeloid-biased hematopoiesis under stress and in aging
GTH Congress 2023 – 67th Annual Meeting of the Society of Thrombosis and Haemostasis Research – The patient as a benchmarkHämostaseologie(2023)
摘要
Introduction Hematopoietic stem and progenitor cells (HSPC) replenish all mature blood cells to meet the host’s adaptive demand. We showed an important role for the endothelial protein C receptor (EPCR) in maintaining HSC quiescence via integrin α4β1 (VLA4), the small GTPase Cdc42 and PAR (protease-activated receptor) 1 in the bone marrow (BM). To discriminate functions of EPCR in anticoagulation versus signaling, we studied EPCRC/S mice carrying a single intracellular point mutation abolishing normal trafficking of EPCR through endo-lysosomal compartments. We assessed the contributions of EPCR signaling to stem cell maintenance by analyzing HSPC during mobilization, myeloablation and aging. Moreover, we compared the phenotype of EPCRC/S and PAR1 mutants with selective protease resistance, namely PAR1R41Q and PAR1R46Q mice.
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关键词
aging,myeloid-biased
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