GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE115903 Query DataSets for GSE115903
Status Public on Nov 28, 2018
Title Understanding Early Stage Myelodysplastic Syndrome Pathobiology
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Delineating key HSC regulators is of significant interest for informing the treatment of hematologic malignancy. While HSC activity is enhanced by overexpression of SKI, the transforming growth factor-beta (TGFβ) signaling antagonist corepressor, its requirement in HSC is unknown. Here we reveal a profound defect in Ski-/- HSC fitness but not specification. Transcriptionally, Ski-/- HSC exhibited striking upregulation of TGFb superfamily signaling and splicing alterations. As these are both common aspects of myelodysplastic-syndrome (MDS) pathobiology with prognostic value, we investigated the role of SKI in MDS. A SKI­-correlated gene signature defines a subset of low-risk MDS patients with active TGFβ signaling and deregulated RNA splicing (e.g. CSF3R). The apparent paradox of Ski-/- HSC sharing molecular aspects of MDS with elevated SKI-mRNA is resolved by miR-21 targeting of SKI in MDS. We conclude that miR-21-mediated loss of SKI contributes to early stage MDS pathogenesis by activating TGFβ signaling and alternative splicing while hindering HSC fitness.
Overall design Single cell RNA seq of transplanted fetal liver-derived hematopoietic stem cells
Contributor(s) Muench DE, Salomonis N, Grimes HL
Citation(s) 30249787
Submission date Jun 17, 2018
Last update date Mar 21, 2019
Contact name H. Leighton Grimes
Phone 513-636-6089
Organization name Cincinnati Childrens Hospital Medical Center
Department Immunobiology
Lab Grimes
Street address 3333 Burnet Ave. MLC 7038
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (94)
GSM3193019 Ski-KO SLAM Cell1
GSM3193020 Ski-KO SLAM Cell2
GSM3193021 Ski-KO SLAM Cell3
BioProject PRJNA476461
SRA SRP150686

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
GSE115903_SkiHSCExp.txt.gz 1.7 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap