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Series GSE180904 Query DataSets for GSE180904
Status Public on Jul 05, 2022
Title STAT1 is essential for hematopoietic stem cell function and maintains a MHC IIhi stem cell subset that resists myeloablation and neoplastic expansion
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Adult hematopoietic stem cells (HSCs) are predominantly quiescent and can be activated in response to acute stress such as infection or cytotoxic insults. STAT1 is a pivotal mediator of interferon (IFN) signaling and is required for IFN-induced HSC proliferation, but the downstream mechanisms remain unclear and in particular little is known about the role of STAT1 in regulating hematopoietic stem/progenitor cells during homeostasis. Here we show that loss of STAT1 alters the steady state hematopoietic stem and progenitor (HSPC) landscape, impairs HSC function in transplantation assays and delays blood cell regeneration following myeloablation. Under steady state conditions STAT1 was essential for several HSC transcriptional programs including expression of genes involved in virus life cycle, a subset of interferon-stimulated genes, MHC class I genes and genes involved in cell cycle arrest. In addition Stat-1 deficient mice lacked a previously unrecognized quiescent subset of homeostatic HSCs with high levels of MHC II expression (MHC IIhi HSCs). This subset was refractory to 5’-FU induced myeloablation and displayed reduced megakaryocytic potential. Mutant calreticulin, which causes increased megakaryopoiesis in human myeloproliferative neoplasms, gave rise to preferential expansion of MHC IIlo HSCs. These data reveal a STAT1 dependent MHC IIhi quiescent HSC subset and show that STAT1 protects HSCs from proliferative exhaustion.
 
Overall design Bone marrow cells were harvested from STAT1KO and WT control mice, single ESLAM HSCs was FACS sorted
 
Contributor(s) Li J, Williams MJ, Park HJ, Bastos HP, Wang X, Wilson NK, Kinston SJ, Göttgens B, Green AR
Citation(s) 35767701
Submission date Jul 27, 2021
Last update date Jul 05, 2022
Contact name Hugo P. Bastos
E-mail(s) hpb29@cam.ac.uk
Organization name Wellcome - MRC Cambridge Stem Cell Institute
Department Haematology
Street address Jeffrey Cheah Biomedical Centre, Puddicombe Way
City Cambridge
ZIP/Postal code CB2 0AW
Country United Kingdom
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (384)
GSM5474466 RBG25878_Plate_1_KO [SLX.14258.i701_i507]
GSM5474467 RBG25879_Plate_1_KO [SLX.14258.i702_i507]
GSM5474468 RBG25876_Plate_1_WT [SLX.14258.i714_i506]
Relations
BioProject PRJNA750055
SRA SRP330031

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
GSE180904_ESLAM_STAT1_QC_filtered_and_normalized.txt.gz 29.0 Mb (ftp)(http) TXT
GSE180904_ESLAM_STAT1_all_raw_counts.txt.gz 5.2 Mb (ftp)(http) TXT
GSE180904_ESLAM_cells_metadata.csv.gz 3.0 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record
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