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Series GSE67609 Query DataSets for GSE67609
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
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.
Overall design Comparison of the phenotypic and molecular properties of normal (Runx1f/f, or WT) versus Runx1 deficient (Mut) hematopoietic stem cells.
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
Phone 267-425-0053
Organization name The Children’s Hospital of Philadelphia
Lab Tan Lab
Street address 4002 Colket Translational Research Building (CTRB) 3501 Civic Center Boulevard
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM1651906 WT1_total_RNA
GSM1651907 WT2_total_RNA
GSM1651908 Mut1_total_RNA
BioProject PRJNA280455
SRA SRP056896

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Supplementary file Size Download File type/resource
GSE67609_Runx1_count_matrix.txt.gz 384.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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