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| Status |
Public on Dec 01, 2010 |
| Title |
Gene expression profiling of ATRA-differentiated wild-type and TG2 knockout NB4 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNAi-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions and their silencing lead to reduced adhesive, migratory and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, 3, 22, 24 and cytokines IL1B and IL8 involved in the development of differentiation syndrome (DS) are expressed at significantly lower levels in TG2-KD NB4 cells than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of DS.
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| Overall design |
We used microarrays to detail the global program of gene expression underlying ATRA-induced differentiation of TG2 knockout NB4 cells.
TG2 knockout NB4 cells were differentiated for 48 and 72 hours in the presence of ATRA and their gene expression profiles were compared to the wild-type cells at the same time points. Undifferentiated wild-type and TG2 knockout NB4 cells were used as untreated controls. Three biological replicates each.
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| Contributor(s) |
Csomos K, Balajthy Z, Nagy I, Fesus L |
| Citation(s) |
20739659 |
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| Submission date |
Aug 18, 2010 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Krisztian Csomos |
| E-mail(s) |
csomosk@dote.hu
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| Organization name |
University of Debrecen
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| Street address |
Egyetem ter 1.
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| City |
Debrecen |
| ZIP/Postal code |
4012 |
| Country |
Hungary |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (18)
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| GSM594067 |
Untreated wild-type NB4, biological rep1 |
| GSM594068 |
Untreated wild-type NB4, biological rep2 |
| GSM594069 |
Untreated wild-type NB4, biological rep3 |
| GSM594070 |
Untreated TG2 knockout NB4, biological rep1 |
| GSM594071 |
Untreated TG2 knockout NB4, biological rep2 |
| GSM594072 |
Untreated TG2 knockout NB4, biological rep3 |
| GSM594073 |
48 hour-treated wild-type NB4, biological rep1 |
| GSM594074 |
48 hour-treated wild-type NB4, biological rep2 |
| GSM594075 |
48 hour-treated wild-type NB4, biological rep3 |
| GSM594076 |
48 hour-treated TG2 knockout NB4, biological rep1 |
| GSM594077 |
48 hour-treated TG2 knockout NB4, biological rep2 |
| GSM594078 |
48 hour-treated TG2 knockout NB4, biological rep3 |
| GSM594079 |
72 hour-treated wild-type NB4, biological rep1 |
| GSM594080 |
72 hour-treated wild-type NB4, biological rep2 |
| GSM594081 |
72 hour-treated wild-type NB4, biological rep3 |
| GSM594082 |
72 hour-treated TG2 knockout NB4, biological rep1 |
| GSM594083 |
72 hour-treated TG2 knockout NB4, biological rep2 |
| GSM594084 |
72 hour-treated TG2 knockout NB4, biological rep3 |
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| Relations |
| BioProject |
PRJNA130897 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23702_RAW.tar |
104.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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