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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 06, 2019 |
| Title |
Mus musculus Gata2 +9.5 Ets C>T transition untreated and 10 days post 5-FU LSK cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The development and function of stem and progenitor cells that produce blood cells are vital in physiology. GATA2 mutations cause immunodeficiency, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). GATA-2 physiological activities necessitate that it be strictly regulated and cell type-specific enhancers fulfill this role. The +9.5 intronic enhancer harbors multiple conserved cis-elements, and germline mutations of these cis-elements are pathogenic in humans. Since mechanisms underlying how GATA2 enhancer disease mutations impact hematopoiesis and pathology are unclear, we generated mouse models of the enhancer mutations. While a multi-motif mutant was embryonic lethal, a single-nucleotide Ets motif mutant was viable and steady-state hematopoiesis was normal. However, the Ets motif mutation abrogated stem/progenitor cell regeneration following stress. These results reveal a new mechanism in human genetics in which a disease mutation inactivates enhancer regenerative activity, while sparing developmental activity. Mutational sensitization to stress that instigates hematopoietic failure constitutes a paradigm for GATA-2-dependent pathogenesis.
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| Overall design |
WT and Gata2 +9.5(Ets)-/- mice were injected with PBS or 250 mg/kg 5-fluorouracil. 10 days post injected, bone marrow was harvested and LSK cells sorted for sequencing. 16 samples were analyzed, using 3-5 replicates per condition.
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| Contributor(s) |
Soukup AA, Zheng Y, Mehta C, Wu J, Liu P, Cao M, Hofmann I, Zhou Y, Zhang J, Johnson KD, Choi K, Keles S, Bresnick EH |
| Citation(s) |
30620726 |
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| Submission date |
Nov 28, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Emery H. Bresnick |
| E-mail(s) |
ehbresni@wisc.edu
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| Phone |
(608) 265-6446
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| Organization name |
University of Wisconsin Madison
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| Department |
Cell and Regenerative Biology
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| Lab |
Bresnick Lab
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| Street address |
4009 WIMR 1111 Highland Ave
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| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53705 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (16)
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| GSM3494801 |
WT + PBS, replicate 4 |
| GSM3494802 |
WT + PBS, replicate 5 |
| GSM3494803 |
Gata2 +9.5(Ets)-/- + PBS, replicate 1 |
| GSM3494804 |
Gata2 +9.5(Ets)-/- + PBS, replicate 2 |
| GSM3494805 |
Gata2 +9.5(Ets)-/- + PBS, replicate 3 |
| GSM3494806 |
Gata2 +9.5(Ets)-/- + PBS, replicate 4 |
| GSM3494807 |
Gata2 +9.5(Ets)-/- + PBS, replicate 5 |
| GSM3494808 |
WT + 5-FU, replicate 1 |
| GSM3494809 |
WT + 5-FU, replicate 2 |
| GSM3494810 |
WT + 5-FU, replicate 3 |
| GSM3494811 |
Gata2 +9.5(Ets)-/- + 5-FU, replicate 1 |
| GSM3494812 |
Gata2 +9.5(Ets)-/- + 5-FU, replicate 2 |
| GSM3494813 |
Gata2 +9.5(Ets)-/- + 5-FU, replicate 3 |
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| Relations |
| BioProject |
PRJNA507449 |
| SRA |
SRP171064 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123080_RAW.tar |
27.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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