github link
Accession IconSRP150686

Understanding Early Stage Myelodysplastic Syndrome Pathobiology

Organism Icon Mus musculus
Sample Icon 94 Downloadable Samples
Technology Badge IconIllumina HiSeq 2500

Submitter Supplied Information

Description
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 (TGFß) 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 TGFß 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 TGFß signaling and alternative splicing while hindering HSC fitness. Overall design: Single cell RNA seq of transplanted fetal liver-derived hematopoietic stem cells
PubMed ID
Total Samples
94
Submitter’s Institution
No associated institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Cell line
Subject
Processing Information
Additional Metadata
No rows found
Loading...