Spatial single cell transcriptomic analysis informs tumor developmental hierarchy of DICER1 syndrome related sarcoma - PubMed
7 hours ago
- #DICER1 syndrome
- #sarcoma origin
- #spatial transcriptomics
- The study focuses on DICER1-related tumor predisposition (DRTP) syndrome, which involves various malignancies, primarily sarcomas in children and young adults, characterized by a defective DICER1 RNase IIIb domain.
- Researchers developed a lineage-traceable mouse model with a hemizygous Dicer1 mutation in Hic1+ mesenchymal stromal cells, leading to renal tumors that mimic human DRTP sarcoma in both histological and molecular aspects.
- Spatial single-cell transcriptomic analysis identified a specific fibroblastic progenitor population (Hic1+Pdgfra+Dpt+Pi16+) near renal collecting ducts, capable of differentiating into rhabdomyoblastic cells or becoming sarcomatous cells.
- Findings from patient samples confirm similar cell states and developmental pathways, revealing a fibroblastic origin for DRTP sarcoma and providing a reliable mouse model for future research.