Activated Protein C promotes Hematopoietic Stem and Progenitor Cell Quiescence and Engraftment

ABSTRACT: Hematopoietic stem cells (HSCs) are the definitive source of all blood cells and replenish them for life. The endothelial protein C receptor (EPCR) which signals via its coreceptor protease-activated receptor 1 (PAR1) is expressed on a subpopulation of highly quiescent HSCs with high engraftment potential after transplantation. We demonstrate that EPCR/PAR1 on human CD34+ hematopoietic stem and progenitor cells (HSPCs) can be activated by both thrombin (THR) and activated protein C (aPC), inducing distinct signaling. PAR1 activation by THR in HSPCs led to Ca2+ flux, phosphorylation of CREB and ERK1/2 and increased glycolysis. In contrast, aPC activated CREB and AKT, but not ERK1/2, Ca2+ flux or metabolic changes. Functionally, stimulation of human CD34+ cells with aPC decreased differentia

SUBMITTER: Simon, J Pöllmann 

PROVIDER: S-SCDT-10_1038-S44321-026-00529-Y | biostudies-other |

REPOSITORIES: biostudies-other