|
| Status |
Public on Oct 04, 2006 |
| Title |
CD34+ and Treatment with UTP and CXCL12 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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
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| 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.
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| |
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| Citation(s) |
17008551 |
| Submission date |
Jun 27, 2006 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Rossella Manfredini |
| E-mail(s) |
manfredini.rossella@unimore.it
|
| Phone |
+390592058065
|
| Organization name |
Centre for Regenerative Medicine
|
| Department |
Life Sciences
|
| Street address |
Via Gottardi 100
|
| City |
Modena |
| ZIP/Postal code |
41100 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
|
| Samples (4)
|
| GSM116403 |
CD34+ Untreated at 24 hours_2 |
| GSM116404 |
CD34+ Treated 10 uM UTP at 24 hours_2 |
| GSM116405 |
CD34+ Treated 150ng/ml CXCL12 at 24 hours |
| GSM116407 |
CD34+ Treated 10 uM UTP and 150ng/ml CXCL12 at 24 hours |
|
| Relations |
| BioProject |
PRJNA96575 |
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