Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37863903.
- Also identified by DOI 10.1038/s41467-023-42371-7 and PMC identifier 10589300.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Atypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-Cre<sup>ERT2</sup>::Smarcb1<sup>flox/flox</sup> model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the NOTCH pathway.
Medical subject headings
- Rhabdoid Tumor
- Brain Neoplasms
- Teratoma