TY  - JOUR
AU  - Beck, Alexander
AU  - Gabler-Pamer, Lisa
AU  - Alencastro Veiga Cruzeiro, Gustavo
AU  - Lambo, Sander
AU  - Englinger, Bernhard
AU  - Shaw, McKenzie L
AU  - Hack, Olivia A
AU  - Liu, Ilon
AU  - Haase, Rebecca D
AU  - de Biagi, Carlos A O
AU  - Baumgartner, Alicia
AU  - Nascimento Silva, Andrezza Do
AU  - Klenner, Marbod
AU  - Freidel, Pia S
AU  - Herms, Jochen
AU  - von Baumgarten, Louisa
AU  - Tonn, Joerg C
AU  - Thon, Niklas
AU  - Bruckner, Katharina
AU  - Madlener, Sibylle
AU  - Mayr, Lisa
AU  - Senfter, Daniel
AU  - Peyrl, Andreas
AU  - Slavc, Irene
AU  - Lötsch, Daniela
AU  - Dorfer, Christian
AU  - Geyregger, Rene
AU  - Amberg, Nicole
AU  - Haberler, Christine
AU  - Mack, Norman
AU  - Schwalm, Benjamin
AU  - Pfister, Stefan
AU  - Korshunov, Andrey
AU  - Baird, Lissa C
AU  - Yang, Edward
AU  - Chi, Susan N
AU  - Alexandrescu, Sanda
AU  - Gojo, Johannes
AU  - Kool, Marcel
AU  - Hovestadt, Volker
AU  - Filbin, Mariella G
TI  - Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.
JO  - Nature cancer
VL  - 6
IS  - 6
SN  - 2662-1347
CY  - London
PB  - Nature Research
M1  - DKFZ-2025-01095
SP  - 1035-1055
PY  - 2025
N1  - #LA:B062# / 2025 Jun;6(6):1035-1055
AB  - Embryonal tumor with multilayered rosettes (ETMR) is a pediatric brain tumor with dismal prognosis. Characteristic alterations of the chromosome 19 microRNA cluster (C19MC) are observed in most ETMR; however, the ramifications of C19MC activation and the complex cellular architecture of ETMR remain understudied. Here we analyze 11 ETMR samples from patients using single-cell transcriptomics and multiplexed spatial imaging. We reveal a spatially distinct cellular hierarchy that spans highly proliferative neural stem-like cells and more differentiated neuron-like cells. C19MC is predominantly expressed in stem-like cells and controls a transcriptional network governing stemness and lineage commitment, as resolved by genome-wide analysis of microRNA-mRNA binding. Systematic analysis of receptor-ligand interactions between malignant cell types reveals fibroblast growth factor receptor and Notch signaling as oncogenic pathways that can be successfully targeted in preclinical models and in one patient with ETMR. Our study provides fundamental insights into ETMR pathobiology and a powerful rationale for more effective targeted therapies.
LB  - PUB:(DE-HGF)16
C6  - pmid:40419763
DO  - DOI:10.1038/s43018-025-00964-9
UR  - https://inrepo02.dkfz.de/record/301587
ER  -