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| Status |
Public on Jul 27, 2015 |
| Title |
Runx1 deficiency decreases ribosome biogenesis and confers stress resistance to hematopoietic stem and progenitor cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating pre-leukemic stem cells that expand in the bone marrow. Here we show that, counter-intuitively, Runx1 deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involves decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins, and binds the ribosomal DNA repeats. Runx1 deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and endoplasmic reticulum stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1 deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs.
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| Overall design |
Comparison of the phenotypic and molecular properties of normal (Runx1f/f, or WT) versus Runx1 deficient (Mut) hematopoietic stem cells.
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| Contributor(s) |
Cai X, Gao L, Teng L, Ge J, Oo ZM, Kumar AR, Gilliland DG, Mason PJ, Tan K, Speck NA |
| Citation(s) |
26165925 |
| Submission date |
Apr 06, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Long Gao |
| E-mail(s) |
gaol3@email.chop.edu
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| Phone |
267-425-0053
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| Organization name |
The Children’s Hospital of Philadelphia
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| Lab |
Tan Lab
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| Street address |
4002 Colket Translational Research Building (CTRB) 3501 Civic Center Boulevard
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA280455 |
| SRA |
SRP056896 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67609_Runx1_count_matrix.txt.gz |
384.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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