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GEO help: Mouse over screen elements for information. |
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| 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 [LK] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| Overall design |
Bone marrow cells were harvested from STAT1KO and WT control mice, lineage negative cKit positive LK cells (lin-cKit+) were sorted
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| Contributor(s) |
Li J, Williams MJ, JPark H, Bastos HP, Wang X, Wilson NK, Göttgens B, Green AR |
| Citation(s) |
35767701 |
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| Submission date |
Jul 27, 2021 |
| Last update date |
Jul 06, 2022 |
| Contact name |
Hugo P. Bastos |
| E-mail(s) |
[email protected]
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| Organization name |
Wellcome - MRC Cambridge Stem Cell Institute
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| Department |
Haematology
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| Street address |
Jeffrey Cheah Biomedical Centre, Puddicombe Way
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0AW |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA750053 |
| SRA |
SRP330029 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180905_RAW.tar |
71.5 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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