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Homo sapiens

ABSTRACT: CD34+ and Treatment with UTP and CXCL12

PROVIDER: PRJNA96575 | ENA |

REPOSITORIES: ENA

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Homo sapiens

Project description:CD34+ and Treatment with UTP

| PRJNA93181 | ENA

CD34+ and Treatment with UTP and CXCL12

Project description:Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and non-peptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key-factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine-triphosphate (ATP) and uridine-triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation of migrating CD34+ cells and increased cell adhesion to fibronectin. In vivo, pre-incubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Gαi) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5’-triphosphatases (GTPase) Rac2 and downstream effectors Rho GTPase–activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the migration of HSCs and their homing to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Gαi proteins and RhoGTPases. Keywords: treatment comparison

2006-10-04 | GSE5168 | GEO

Transcription profiling of human CD34+ cells and treatment with UTP and CXCL12

Project description:Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and non-peptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key-factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine-triphosphate (ATP) and uridine-triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation of migrating CD34+ cells and increased cell adhesion to fibronectin. In vivo, pre-incubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (GÎ±i) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5â-triphosphatases (GTPase) Rac2 and downstream effectors Rho GTPaseâactivated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the migration of HSCs and their homing to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving GÎ±i proteins and RhoGTPases. Experiment Overall Design: Highly purified CD34+ cells from 6 healthy donors were seeded at 1000000 cells/ml in serum free medium (EX vivo 15) w/o cytokines and treated with 10 mM UTP, 150ng/ml CXCL12, or 10 mM UTP plus 150ng/ml CXCL12 respectively for 24 hours. As a control, CD34+ untreated cells were maintained in the same culture conditions at the same time.

2008-06-13 | E-GEOD-5168 | biostudies-arrayexpress