Pten cell autonomously regulates HSC mobilization and function via G-CSF independent mechanisms
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61655 | GEO | 2015/09/22
SECONDARY ACCESSION(S): PRJNA261781
REPOSITORIES: GEO
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Project description:gene expression in control, Pten deficient and G-CSF mobilized hematiopoietic stem cells HSCs isolated from control bone marrow, Pten deficient spleens and G-CSF treated spleens
2015-09-22 | E-GEOD-61655 | biostudies-arrayexpress
Project description:Treatment of healthy donors with G-CSF and dexamethasone, results in sufficient number of circulating granulocytes to prepare granulocyte concentrates for clinical purposes. Granulocytes obtained this way demonstrate relatively normal functional behavior combined with a prolonged life span. To study the influence of mobilizing agents on granulocytes, we used oligonucleotide microarrays to identify genes that are differentially expressed in mobilized granulocytes as compared to control ones. Keywords: mobilized granulocytes, G-CSF/dexamethasone treated granulocytes Granulocytes were isolated from three individuals before (control situation) and 18 hours after treatment with G-CSF&dexamethasone; part of the control cells was cultured overnight in HBSS medium with or without addition of G-CSF and dexamethasone. Total RNA from each experimental condition was compared to pooled RNA of control granulocytes.
2010-04-03 | E-GEOD-12841 | biostudies-arrayexpress
Project description:Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic progenitors stem cells (HPSC) with high repopulating capacity and mobilization is the optimal approach for achieving this goal. We performed a clinical study to investigate safety and efficacy of G-CSF+AMD3100 mobilization in four adult with β-thalassemia to reach a cell dose of â¥8x106 CD34+cells/Kg and to characterize the CD34+cell populations mobilized before and after plerixafor administration. The procedure resulted well-tolerated in all patients. Three of the four patients reached the target cell dose or more in single-apheresis collections, even one patient where a significant dose reduction of G-CSF was imposed due to early hyperleukocytosis. A significant increase in the number of circulating CD34+ cells/µl (12.1± 8.2 fold), and in the frequency of the more primitive CD34+/CD133+/CD38- cells (1.7±0.7 fold) was unanimously observed after AMD3100 addiction. Intraindividual comparison of gene expression profile of CD34+ cells mobilized with G-CSF versus G-CSF+ AMD3100 highlighted a different expression pattern of genes involved in the processes of HSC/stroma adhesion, homing, cell motility and transcription regulation. Overall, the safety profile, the yield, and the expression of genes that potentially promote superior engraftment depict G-CSF+AMD3100 mobilized HSC as optimal graft source for β-thalassemia gene therapy One experiment performed on purified CD34+ PBPC of the same patient 1 after mobilization with G-CSF + Plerixafor , and after mobilization with G-CSF alone. Universal Human Reference RNA (Stratagene, La Jolla, CA), was used as reference.
2017-04-28 | E-GEOD-70219 | biostudies-arrayexpress
Project description:Granulocyte-colony stimulating factor (G-CSF) is used to boost granulocyte counts in immunocompromised patients, but its effects on the immune system may be counter productive. We tested the hypothesis that G-CSF mobilized peripheral blood stem cell (PBSC) products are immunologically down regulated based on gene microarray analysis. Ten peripheral blood samples from normal donors for allogeneic PBSC transplantation were obtained before and after administration of G-CSF and tested on Affymetrix Human U133 Plus 2.0 GeneChip® microarrays. Significant changes in gene expression after G-CSF mobilization were reported by controlling the false discovery rate at 5%. Immune-related genes were isolated from the data set and categorized according to probe set annotations and a thorough, independent literature search. We found that G-CSF up-regulated inflammatory and neutrophil activation pathway gene expression; however, adaptive immune-related gene expression, such as antigen presentation, co-stimulation, T cell activation and cytolytic effector pathways, were generally down-regulated. Thus, despite significant increases in stem cells, lymphocytes and antigen presenting cells, G-CSF mobilized PBSC allografts exhibit a suppressive adaptive immune-related gene expression profile. Our data provides an explanation for the potentially immunosuppressive effects observed after G-CSF administration. Keywords: PBSCT, G-CSF, microarray, gene expression
2007-08-09 | GSE7400 | GEO
Project description:Treatment of healthy donors with G-CSF and dexamethasone, results in sufficient number of circulating granulocytes to prepare granulocyte concentrates for clinical purposes. Granulocytes obtained this way demonstrate relatively normal functional behavior combined with a prolonged life span. To study the influence of mobilizing agents on granulocytes, we used oligonucleotide microarrays to identify genes that are differentially expressed in mobilized granulocytes as compared to control ones. Keywords: mobilized granulocytes, G-CSF/dexamethasone treated granulocytes
2009-09-09 | GSE12841 | GEO
Project description:Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic progenitors stem cells (HPSC) with high repopulating capacity and mobilization is the optimal approach for achieving this goal. We performed a clinical study to investigate safety and efficacy of G-CSF+AMD3100 mobilization in four adult with β-thalassemia to reach a cell dose of ≥8x106 CD34+cells/Kg and to characterize the CD34+cell populations mobilized before and after plerixafor administration. The procedure resulted well-tolerated in all patients. Three of the four patients reached the target cell dose or more in single-apheresis collections, even one patient where a significant dose reduction of G-CSF was imposed due to early hyperleukocytosis. A significant increase in the number of circulating CD34+ cells/µl (12.1± 8.2 fold), and in the frequency of the more primitive CD34+/CD133+/CD38- cells (1.7±0.7 fold) was unanimously observed after AMD3100 addiction. Intraindividual comparison of gene expression profile of CD34+ cells mobilized with G-CSF versus G-CSF+ AMD3100 highlighted a different expression pattern of genes involved in the processes of HSC/stroma adhesion, homing, cell motility and transcription regulation. Overall, the safety profile, the yield, and the expression of genes that potentially promote superior engraftment depict G-CSF+AMD3100 mobilized HSC as optimal graft source for β-thalassemia gene therapy
2017-04-28 | GSE70219 | GEO
Project description:CD34+ hematopoietic stem and progenitor cells were isolated immunomagnetically from patients with multiple myeloma during chemotherapy and G-CSF-induced mobilization. Patients received either unconjugated G-CSF (n=9) or polyethylenglykol (PEG)-conjugated G-CSF (n=7). From each patient only one sample was analyzed. Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays according to manufacturer's instructions. Following quality control and normalization 9 samples of G-CSF-mobilized CD34+ cells were compared with 7 samples of PEG-G-CSF-mobilized cells were compared by significance analysis of microarrays (SAM). The aim was to figure out transcriptional differences resulting from various pharmacokinetics of the same drug (G-CSF: fluctuating serum levels; PEG-G-CSF: continously high serum levels). Peripheral blood stem and progenitor cells (PBSC) are widely used for autologous and allogeneic hematopoietic stem cell transplantation. PBSC can be mobilized into the peripheral blood using cytokines, cytotoxic chemotherapy or a combination of both. Granulocyte colony stimulating factor (G-CSF) has become the most commonly administered cytokine for PBSC mobilization because of its high potency and lack of serious toxicity. Recently, a modified form of recombinant human G-CSF has been introduced. This new compound is pegylated G-CSF (Peg-G-CSF) which possesses a substantially longer half-life than the unconjugated drug because of its reduced renal excretion and therefore provides the basis for continuous G-CSF serum-levels after a single injection. The use of Peg-G-CSF in patients who had received a cytotoxic chemotherapy was accompanied by mobilization kinetics different from those observed in patients who had received unconjugated G-CSF. In particular, more rapid leukocyte recovery and occurrence of CD34-positive cells in the peripheral blood was seen. These findings are presumably related to the more even and continuously high serum level of G-CSF maintained by Peg-G-CSF. Using microarray technology and functional assays, we examined whether pegylation of G-CSF and its different pharmacokinetics results in addition to an earlier leucocyte recovery in transcriptional and functional changes in CD34+ cells obtained from patients who had received either G-CSF or Peg-G-CSF following a standard cytotoxic chemotherapy for PBSC mobilisation. CD34+ hematopoietic stem and progenitor cells were isolated immunomagnetically from patients with multiple myeloma during chemotherapy and G-CSF-induced mobilization. Patients received either unconjugated G-CSF (n=9) or polyethylenglykol (PEG)-conjugated G-CSF (n=7). Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays. Following quality control and normalization differentially expressed genes were identified by significance analysis of microarrays (SAM). Comparing both groups 339 genes were significantly differentially expressed (q value <5%; fold change > 1.2). Peg-G-CSF-mobilized CD34+ cells showed an expression pattern of more early progenitor cells as early stem cell markers such as HOX genes were higher expressed and differentiation-associated genes were lower expressed in comparison with G-CSF-mobilized cells. Moreover, Peg-G-CSF-mobilized CD34+ cells had a greater expression level of cell-cycle-promoting genes suggesting a greater cycle activity of these cells. In conclusion, despite the similar active drug component different pharmacokinetics of Peg-G-CSF and G-CSF result in distinct molecular phenotypes reflecting different functional characteristics.
2007-10-26 | E-GEOD-4688 | biostudies-arrayexpress
Project description:Plerixafor (AMD3100) and G-CSF mobilize peripheral blood stem cells (PBSCs) by different mechanisms. A rhesus macaque model was used to compare plerixafor and G-CSF-mobilized CD34+ cells. Three PBSC concentrates were collected from 3 macaques treated with G-CSF, plerixafor, or plerixafor plus G-CSF. CD34+ cells were isolated by immunoselection and were analyzed by global gene and micro RNA (miR) expression microarrays. Unsupervised hierarchical clustering of the gene expression data separated the CD34+ cells into three groups based on mobilization regimen. Plerixafor-mobilized cells were enriched for B cells, T cells and mast cells genes and G-CSF-mobilized cells were enriched for neutrophils, and mononuclear phagocytes (MPs) genes. Genes up-regulated in plerixafor plus G-CSF-mobilized CD34+ cells included many that were not up-regulated by either agent alone. Two hematopoietic progenitor cell miR, miR-10 and miR-126, and a dendritic cell miR, miR-155, were up-regulated in G-CSF-mobilized CD34+ cells. A pre-B cell acute lymphocytic leukemia miR, miR-143-3p, and a T cell miR, miR-143-5p, were up-regulated in plerixafor plus G-CSF-mobilized cells. The composition of CD34+ cells is dependent on the mobilization protocol. Plerixafor-mobilized CD34+ cells include more B, T, and mast cell precursors while G-CSF-mobilized cells have more neutrophil and MP precursors.
2009-12-05 | GSE16936 | GEO
Project description:Plerixafor (AMD3100) and G-CSF mobilize peripheral blood stem cells (PBSCs) by different mechanisms. A rhesus macaque model was used to compare plerixafor and G-CSF-mobilized CD34+ cells. Three PBSC concentrates were collected from 3 macaques treated with G-CSF, plerixafor, or plerixafor plus G-CSF. CD34+ cells were isolated by immunoselection and were analyzed by global gene and micro RNA (miR) expression microarrays. Unsupervised hierarchical clustering of the gene expression data separated the CD34+ cells into three groups based on mobilization regimen. Plerixafor-mobilized cells were enriched for B cells, T cells and mast cells genes and G-CSF-mobilized cells were enriched for neutrophils, and mononuclear phagocytes (MPs) genes. Genes up-regulated in plerixafor plus G-CSF-mobilized CD34+ cells included many that were not up-regulated by either agent alone. Two hematopoietic progenitor cell miR, miR-10 and miR-126, and a dendritic cell miR, miR-155, were up-regulated in G-CSF-mobilized CD34+ cells. A pre-B cell acute lymphocytic leukemia miR, miR-143-3p, and a T cell miR, miR-143-5p, were up-regulated in plerixafor plus G-CSF-mobilized cells. The composition of CD34+ cells is dependent on the mobilization protocol. Plerixafor-mobilized CD34+ cells include more B, T, and mast cell precursors while G-CSF-mobilized cells have more neutrophil and MP precursors. Three rhesus macaques were given all three mobilization protocols and PBSCs were collected from each of these three animals. Two monkeys were given plerixafor first, one was given G-CSF first and all three were given plerixafor plus G-CSF last. This resulted in 6 samples (CD34+ and CD34- cells from each of the 3 mobilizations) from each of the 3 individual animals (biological replicates).
2009-12-04 | E-GEOD-16936 | biostudies-arrayexpress
Project description:Peripheral blood stem and progenitor cells (PBSC) are widely used for autologous and allogeneic hematopoietic stem cell transplantation. PBSC can be mobilized into the peripheral blood using cytokines, cytotoxic chemotherapy or a combination of both. Granulocyte colony stimulating factor (G-CSF) has become the most commonly administered cytokine for PBSC mobilization because of its high potency and lack of serious toxicity. Recently, a modified form of recombinant human G-CSF has been introduced. This new compound is pegylated G-CSF (Peg-G-CSF) which possesses a substantially longer half-life than the unconjugated drug because of its reduced renal excretion and therefore provides the basis for continuous G-CSF serum-levels after a single injection. The use of Peg-G-CSF in patients who had received a cytotoxic chemotherapy was accompanied by mobilization kinetics different from those observed in patients who had received unconjugated G-CSF. In particular, more rapid leukocyte recovery and occurrence of CD34-positive cells in the peripheral blood was seen. These findings are presumably related to the more even and continuously high serum level of G-CSF maintained by Peg-G-CSF. Using microarray technology and functional assays, we examined whether pegylation of G-CSF and its different pharmacokinetics results in addition to an earlier leucocyte recovery in transcriptional and functional changes in CD34+ cells obtained from patients who had received either G-CSF or Peg-G-CSF following a standard cytotoxic chemotherapy for PBSC mobilisation. CD34+ hematopoietic stem and progenitor cells were isolated immunomagnetically from patients with multiple myeloma during chemotherapy and G-CSF-induced mobilization. Patients received either unconjugated G-CSF (n=9) or polyethylenglykol (PEG)-conjugated G-CSF (n=7). Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays. Following quality control and normalization differentially expressed genes were identified by significance analysis of microarrays (SAM). Comparing both groups 339 genes were significantly differentially expressed (q value <5%; fold change > 1.2). Peg-G-CSF-mobilized CD34+ cells showed an expression pattern of more early progenitor cells as early stem cell markers such as HOX genes were higher expressed and differentiation-associated genes were lower expressed in comparison with G-CSF-mobilized cells. Moreover, Peg-G-CSF-mobilized CD34+ cells had a greater expression level of cell-cycle-promoting genes suggesting a greater cycle activity of these cells. In conclusion, despite the similar active drug component different pharmacokinetics of Peg-G-CSF and G-CSF result in distinct molecular phenotypes reflecting different functional characteristics. Keywords: ordered
2006-05-03 | GSE4688 | GEO