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Status
Public on Aug 09, 2007
Title
Hematopoietic stem cell mobilization with G-CSF (gene expression profiling)
Organism
Homo sapiens
Experiment type
Expression profiling by array
Summary
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
Overall design
This study was approved by the University of Florida Institutional Review Board. Five healthy donors (A-E) for allogeneic PBSC transplantation consented and were mobilized with rHu G-CSF at 10µ/kg/day for five days. Approximately 4mL of venous blood was collected before (Pre-G-CSF) and after (Post-G-CSF) mobilization. Whole blood leukocyte RNA was purified from each sample and used to generate cRNAs which were subsequently hybridized onto Affymetrix Human U133 Plus 2.0 GeneChip® microarrays. Representative genes were successfully validated with quantitative RT-PCR.
Contributor(s)
Buzzeo M , Reddy V
Citation(s)
17761290
Submission date
Mar 29, 2007
Last update date
Mar 25, 2019
Contact name
Matthew Buzzeo
E-mail(s)
[email protected]
Organization name
University of South Florida College of Medicine
Street address
12901 Bruce B. Downs Blvd
City
Tampa
State/province
FL
ZIP/Postal code
33612
Country
USA
Platforms (1)
GPL570
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (10)
Relations
BioProject
PRJNA97893
Significantly-regulated genes post-GCSF mobilization: Annotated genes (FDR 5%) header descriptions
Probe_ID
Affymetrix U133 Plus 2.0 Array (ie, GEO Platform GPL570) probe set IDs
Gene Symbol
A gene symbol, when one is available (from UniGene)
Gene Title
Title of Gene represented by the probe set
FC (Log2)
P value (ANCOVA)
p-values associated with analysis of covariance
Affymetrix GO Biological Process Description
Gene Ontology Biological Process Description
Data table
Probe_ID
Gene Symbol
Gene Title
FC (Log2)
P value (ANCOVA)
Affymetrix GO Biological Process Description
219669_at
CD177
CD177 molecule
630.41
0.0001
---
231122_x_at
ZDHHC19
zinc finger, DHHC-type containing 19
326.55
0.0003
---
212768_s_at
OLFM4
olfactomedin 4
203.49
0.0008
---
207329_at
MMP8
matrix metallopeptidase 8 (neutrophil collagenase)
145.65
0.0010
peptidoglycan metabolism /// proteolysis /// collagen catabolism /// proteolysis
226804_at
FAM20A
family with sequence similarity 20, member A
97.98
0.0007
---
231688_at
---
Transcribed locus
90.93
0.0010
---
208470_s_at
HP /// HPR
haptoglobin /// haptoglobin-related protein
68.15
0.0019
proteolysis /// iron ion homeostasis /// defense response /// mRNA processing /// cell cycle /// mitosis /// RNA splicing /// cell division /// nuclear mRNA splicing, via spliceosome /// electron transport
216331_at
ITGA7
integrin, alpha 7
61.85
0.0000
cell adhesion /// homophilic cell adhesion /// cell-matrix adhesion /// integrin-mediated signaling pathway /// muscle development /// regulation of cell shape /// blood vessel morphogenesis
206871_at
ELA2
elastase 2, neutrophil
60.26
0.0014
proteolysis /// calcium ion homeostasis /// response to UV /// protein catabolism /// anti-inflammatory response /// positive regulation of MAPK activity /// negative regulation of chemokine biosynthesis /// negative regulation of interleukin-8 biosynthesis /// positive regulation of interleukin-8 biosynthesis /// positive regulation of smooth muscle cell proliferation /// negative regulation of inflammatory response /// negative regulation of chemotaxis
1553952_at
ZDHHC19
zinc finger, DHHC-type containing 19
56.55
0.0011
---
225016_at
APCDD1
adenomatosis polyposis coli down-regulated 1
53.94
0.0009
---
204636_at
COL17A1
collagen, type XVII, alpha 1
50.58
0.0000
electron transport /// phosphate transport /// cell-matrix adhesion /// epidermis development
207269_at
DEFA4
defensin, alpha 4, corticostatin
50.00
0.0009
xenobiotic metabolism /// defense response /// defense response to bacterium /// defense response to fungus
212531_at
LCN2
lipocalin 2 (oncogene 24p3)
44.30
0.0010
transport
209663_s_at
ITGA7
integrin, alpha 7
37.97
0.0007
cell adhesion /// homophilic cell adhesion /// cell-matrix adhesion /// integrin-mediated signaling pathway /// muscle development /// regulation of cell shape /// blood vessel morphogenesis
1553518_at
DEFT1P
defensin, theta 1 pseudogene
34.21
0.0006
---
220570_at
RETN
resistin
33.71
0.0000
biological_process
229230_at
OSTalpha
organic solute transporter alpha
31.20
0.0010
---
207341_at
PRTN3
proteinase 3 (serine proteinase, neutrophil, Wegener granulomatosis autoantigen)
30.41
0.0027
proteolysis /// positive regulation of cell proliferation /// collagen catabolism
223767_at
GPR84
G protein-coupled receptor 84
29.88
0.0003
signal transduction /// G-protein coupled receptor protein signaling pathway /// biological_process
Total number of rows: 4501 Table truncated, full table size 702 Kbytes .Significantly-regulated genes post-GCSF mobilization: Immune-related genes (FDR 5%) header descriptions
Probe_ID
Affymetrix U133 Plus 2.0 Array (ie, GEO Platform GPL570) probe set IDs
Gene Symbol
A gene symbol, when one is available (from UniGene)
Gene Title
Title of Gene represented by the probe set
FC (Log2)
P value (ANCOVA)
p-values associated with analysis of covariance
Affymetrix GO Biological Process Description
Gene Ontology Biological Process Description
Data table
Probe_ID
Gene Symbol
Gene Title
FC (Log2)
P value (ANCOVA)
Affymetrix GO Biological Process Description
219669_at
CD177
CD177 molecule
630.41
0.0001
---
207329_at
MMP8
matrix metallopeptidase 8 (neutrophil collagenase)
145.65
0.0010
peptidoglycan metabolism /// proteolysis /// collagen catabolism /// proteolysis
208470_s_at
HP /// HPR
haptoglobin /// haptoglobin-related protein
68.15
0.0019
proteolysis /// iron ion homeostasis /// defense response /// nuclear mRNA splicing, via spliceosome /// mRNA processing /// cell cycle /// mitosis /// cell division
216331_at
ITGA7
integrin, alpha 7
61.85
0.0000
cell adhesion /// homophilic cell adhesion /// cell-matrix adhesion /// integrin-mediated signaling pathway /// muscle development /// regulation of cell shape
206871_at
ELA2
elastase 2, neutrophil
60.26
0.0014
proteolysis /// calcium ion homeostasis /// response to UV /// protein catabolism /// anti-inflammatory response /// positive regulation of MAPK activity /// negative regulation of chemokine biosynthesis /// negative regulation of interleukin-8 biosynthesis /// positive regulation of interleukin-8 biosynthesis /// positive regulation of smooth muscle cell proliferation /// negative regulation of inflammatory response /// negative regulation of chemotaxis
207269_at
DEFA4
defensin, alpha 4, corticostatin
50.00
0.0009
xenobiotic metabolism /// response to pest, pathogen or parasite /// defense response to bacteria /// defense response to fungi /// defense response
209663_s_at
ITGA7
integrin, alpha 7
37.97
0.0007
cell adhesion /// homophilic cell adhesion /// cell-matrix adhesion /// integrin-mediated signaling pathway /// muscle development /// regulation of cell shape
206676_at
CEACAM8
carcinoembryonic antigen-related cell adhesion molecule 8
27.98
0.0026
immune response
231771_at
GJB6
gap junction protein, beta 6 (connexin 30)
26.58
0.0003
immune response /// cell communication /// sensory perception of sound /// sensory perception of sound
203949_at
MPO
myeloperoxidase
26.45
0.0031
anti-apoptosis /// defense response /// response to oxidative stress /// hydrogen peroxide catabolism /// response to oxidative stress
206697_s_at
HP
haptoglobin
26.38
0.0016
proteolysis /// iron ion homeostasis /// defense response /// nuclear mRNA splicing, via spliceosome /// mRNA processing /// cell cycle /// mitosis /// cell division
205557_at
BPI
bactericidal/permeability-increasing protein
23.09
0.0002
immune response /// response to pest, pathogen or parasite /// defense response to bacteria
203948_s_at
MPO
myeloperoxidase
22.39
0.0009
anti-apoptosis /// defense response /// response to oxidative stress /// hydrogen peroxide catabolism /// response to oxidative stress
205653_at
CTSG
cathepsin G
15.36
0.0016
proteolysis /// immune response /// proteolysis
209772_s_at
CD24
CD24 molecule
14.57
0.0008
humoral immune response
207384_at
PGLYRP1
peptidoglycan recognition protein 1
13.81
0.0022
peptidoglycan catabolism /// response to pest, pathogen or parasite /// detection of bacteria /// innate immune response /// defense response to Gram-positive bacteria /// immune response /// defense response to bacteria /// immune response
219403_s_at
HPSE
heparanase
12.16
0.0001
proteoglycan metabolism /// inflammatory response
208650_s_at
CD24 /// LOC647456
CD24 molecule /// hypothetical protein LOC647456
9.72
0.0011
humoral immune response
1555643_s_at
LILRA5
leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 5
9.55
0.0012
---
203936_s_at
MMP9
matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)
9.53
0.0026
peptidoglycan metabolism /// proteolysis /// macrophage differentiation /// collagen catabolism /// proteolysis
Total number of rows: 490 Table truncated, full table size 101 Kbytes .
Supplementary file
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File type/resource
GSE7400_RAW.tar
46.0 Mb
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Processed data are available on Series record
Processed data included within Sample table