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| Status |
Public on Aug 02, 2016 |
| Title |
DNA damage-induced HSPC failure depends on ROS accumulation downstream of IFN-1 signaling and Bid mobilization |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Targeted mouse mutants with inactivated Mixed-Lineage-Leukemia-5 (Mll5, MGI:1924825) alleles exhibit numerical, cell cycle and functional abnormalities in their hematopoietic stem and progenitor cell (HSPC) compartments, including hyper-proliferation of otherwise quiescent hematopoietic stem cells, lack of long-term reconstitution potential and profound radiation sensitivity. Most of the HSPC defects are secondary to increased levels of DNA damage and intracellular accumulation of reactive oxygen species (ROS). To obtain first insights into underlying molecular mechanisms, we performed Affymetrix gene chip analysis using total RNA isolated from FACS-sorted Lin-Sca1+Kit+ (LSK) cells of Mll5+/+ and Mll5-/- mice, both with and without prior long-term treatment with the ROS quencher N-Acetyl-L-Cysteine (NAC). As key finding, microarray data revealed elevated hybridization signals for several transcripts of known or putative IFN-1 target genes in LSK cells from Mll5-/- mice irrespective of NAC-treatment. In fact, comprehensive gene set enrichment analysis identified a number of gene sets closely associated with interferon responses that were significantly affected in Mll5-/- LSK cells.
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| Overall design |
RNA was isolated from FACS-sorted Lin-Sca1+Kit+ (LSK) cells of Mll5+/+ and Mll5-/- mice, both with and without prior long-term treatment with the ROS quencher N-Acetyl-L-Cysteine (NAC)
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| Contributor(s) |
Mulaw MA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 01, 2016 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Medhanie Assmelash Mulaw |
| E-mail(s) |
medhanie.mulaw@uni-ulm.de
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| Organization name |
University of Ulm
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| Street address |
Albert-Einstein-Allee 11
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| City |
Ulm |
| ZIP/Postal code |
89081 |
| Country |
Germany |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA336057 |
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