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Series GSE112842 Query DataSets for GSE112842
Status Public on May 28, 2018
Title A system of checks and balances: an ERK-dependent feedback mechanism prevents hematopoietic stem cell exhaustion
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hematopoietic stem cells (HSC) sustain hematopoiesis throughout life, exiting dormancy to replenish homeostatic or acute cell loss in the peripheral blood. HSC activation is supported by PI3-Kinase/AKT/mTORC1 pathway, which promotes mitochondrial expansion, oxidative phosphorylation, and reactive oxygen species production. Activated HSCs must return to dormancy to prevent exhaustion and bone marrow failure, but the cell-intrinsic mechanisms underlying this transition are unknown. Here we identify an ERK-dependent, rate-limiting feedback mechanism that controls the fitness of the HSC compartment. We show that the MEK/ERK and PI3-Kinase pathways are synchronously deployed in HSC during emergency hematopoiesis, and that feedback phosphorylation of MEK1 by activated ERK is required to constrain AKT/mTORC1 activation. Genetic or chemical ablation of this feedback tilts the balance between HSC dormancy and activation, increasing the output of differentiated cells and accelerating HSC exhaustion. MEK inhibitors developed for cancer therapy may thus be useful to modulate HSC activation.
Overall design RNA-seq: WT (n=3+1 technical) vs. KO (n=3) HSCs + 5-FU-treated WT (n=4) vs. KO (n=3) HSCs; 13 RNA-seq datasets total
Web link
Contributor(s) Baumgartner C, Toifl S, Farlik M, Halbritter F, Scheicher R, Fischer I, Sexl V, Bock C, Baccarini M
Citation(s) 29804890
Submission date Apr 09, 2018
Last update date Feb 11, 2019
Contact name Christoph Bock
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (13)
GSM3084905 HSC_5FU_Treated_KO_A5
GSM3084906 HSC_5FU_Treated_KO_A6
GSM3084907 HSC_5FU_Treated_KO_A8
BioProject PRJNA449288

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE112842_baumgartner_data_norm.csv.gz 1.2 Mb (ftp)(http) CSV
Raw data are available in SRA
Processed data are available on Series record

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