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Series GSE12067 Query DataSets for GSE12067
Status Public on Jun 01, 2009
Title IL-3 coordination of myeloblast function by modulating mRNA stability
Organism Mus musculus
Experiment type Expression profiling by array
Summary The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. We used kinetic microarray, Northern Blotting and bioinformatics analysis of IL-3 dependent myeloblasts to determine whether IL-3 acts in part by regulating the rate of turnover of mRNA transcripts in specific functional pathways. Our results indicate that exposure of myeloblasts to IL-3 causes immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Examples include transcripts associated with proliferation and leukemic transformation (pik3cd, myb, pim-1), hematopoietic development (cited2), differentiation control (cdkn1a) and RNA processing (BRF1, BRF2). A domain in the 3’-utr of IL-6 that mediates IL-3 responsiveness contains AU-rich elements that bind proteins known to modulate mRNA stability, however a known destabilizing protein (AUF1) is shown not to mediate degradation in the absence of IL-3. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of this network of transcripts could contribute to growth patterns observed in leukemia.
 
Overall design Cells were exposed to actinomycin D to block transcription for 0, 2 or 4 hours. The cytokine IL-3 was added after actinomycin D either at a high (1 ng/ml) or low (10 pg/ml) concentration. The effect of cytokine on transcript decay rates was therefore determined. There were five determinations per experiment (0 hour, and 2 hr and 4 hours, the latter two time points at both high and at low IL3); two independent experiments are represented (10 microarray analyses in total).
 
Contributor(s) Ernst J, Ghanem L, Bar-Joseph Z, McNamara M, Steinman RA
Citation(s) 19829692
Submission date Jul 10, 2008
Last update date May 04, 2018
Contact name Richard A Steinman
E-mail(s) steinman@pitt.edu
Phone 412 6233237
Fax 412 6237768
Organization name University of Pittsburgh
Department Medicine
Lab 2.18 Hillman Cancer Center
Street address 5117 Centre Avenue
City Pittsburgh
State/province PA
ZIP/Postal code 15213
Country USA
 
Platforms (1)
GPL8321 [Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array
Samples (10)
GSM304665 32D cells time 0 after actinomycin D Experiment 2
GSM304666 32D cells time 2 hr after actinomycin D, High IL3, Experiment 2
GSM304667 32D cells time 4 hr after actinomycin D, High IL3, Experiment 2
Relations
BioProject PRJNA113315

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE12067_RAW.tar 17.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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