Transcriptomics

Dataset Information

355

Runx1 deficiency decreases ribosome biogenesis and confers stress resistance to hematopoietic stem and progenitor cells


ABSTRACT: 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. Comparison of the phenotypic and molecular properties of normal (Runx1f/f, or WT) versus Runx1 deficient (Mut) hematopoietic stem cells.

ORGANISM(S): Mus musculus  

SUBMITTER: Philip J Mason   Xiongwei Cai  Kai Tan  Jingping Ge  D G Gilliland  Ashish R Kumar  Nancy A Speck  Long Gao  Li Teng  Zaw M Oo 

PROVIDER: E-GEOD-67609 | ArrayExpress | 2015-07-27

SECONDARY ACCESSION(S): SRP056896GSE67609PRJNA280455

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells.

Cai Xiongwei X   Gao Long L   Teng Li L   Ge Jingping J   Oo Zaw Min ZM   Kumar Ashish R AR   Gilliland D Gary DG   Mason Philip J PJ   Tan Kai K   Speck Nancy A NA  

Cell stem cell 20150709 2


The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating preleukemic stem cells that expand in the bone marrow. Here we show, counterintuitively, that 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 involved decreased levels of rRNA and many mRNAs encoding ribosome proteins.  ...[more]

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