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E-GEOD-51107 - Gene expression profiles of murine Runx1;Runx3 double deficient cKit+Sca1+Lin- hematopoietic stem/progenitor cells

Status
Released on 26 August 2014, last updated on 1 September 2014
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (7)
Description
The RUNX genes encode for transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here we show that Runx1;Runx3 double knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes like Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independent of CBFβ, suggesting non-transcriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes development of leukemias and other cancers. 6 mice were analyzed in this study. 3 Runx1;Runx3 double knockout cKit+Sca1+Lin- hematopoietic stem/progenitor cells were compared with their wild type littermate controls. RNA was isolated from 3 independent Runx1;Runx3 WT KSL samples, each pooled from 3 Runx1;Runx3 WT mice, and 3 independent Runx1;Runx3 DKO KSL samples, using the RNeasy Micro Kit (QIAgen). RNA integrity and quantity was assessed using the Agilent 2000 Bioanalyzer system. 3 μg to 5 μg RNA was processed using WT-Ovation Pico RNA Amplification System (NuGEN) paired with the WT-Ovation Exon Module and FL-Ovation cDNA Biotin Module (NuGEN). A detailed protocol in the user’s guide kit was used without modification. cDNA were prepared for hybridization on GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix) according to the instructions in GeneChip Hybridization Wash and Stain Kit for ST arrays (Affymetrix). Microarray hybridization, scanning and preliminary MAS 5.0 normalizations were completed at the A*STAR Biopolis Shared Facilities (BSF).
Experiment type
transcription profiling by array 
Contacts
Motomi Osato
Citation
Disruption of Runx1 and Runx3 Leads to Bone Marrow Failure and Leukemia Predisposition due to Transcriptional and DNA Repair Defects. Wang CQ, Krishnan V, Tay LS, Chin DW, Koh CP, Chooi JY, Nah GS, Du L, Jacob B, Yamashita N, Lai SK, Tan TZ, Mori S, Tanuichi I, Tergaonkar V, Ito Y, Osato M. , PMID:25066130
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-51107.idf.txt
Sample and data relationshipE-GEOD-51107.sdrf.txt
Raw data (1)E-GEOD-51107.raw.1.zip
Processed data (1)E-GEOD-51107.processed.1.zip
Array designA-AFFY-130.adf.txt
Links