Journal Article

DKFZ-2025-01095

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.

Beck, A. ; Gabler-Pamer, L. ; Alencastro Veiga Cruzeiro, G. ; Lambo, S.DKFZ* ; Englinger, B. ; Shaw, M. L. ; Hack, O. A. ; Liu, I. ; Haase, R. D. ; de Biagi, C. A. O. ; Baumgartner, A. ; Nascimento Silva, A. D. ; Klenner, M. ; Freidel, P. S. ; Herms, J. ; von Baumgarten, L.DKFZ* ; Tonn, J. C.DKFZ* ; Thon, N.DKFZ* ; Bruckner, K. ; Madlener, S. ; Mayr, L. ; Senfter, D. ; Peyrl, A. ; Slavc, I. ; Lötsch, D. ; Dorfer, C. ; Geyregger, R. ; Amberg, N. ; Haberler, C. ; Mack, N.DKFZ* ; Schwalm, B.DKFZ* ; Pfister, S.DKFZ* ; Korshunov, A.DKFZ* ; Baird, L. C. ; Yang, E. ; Chi, S. N. ; Alexandrescu, S. ; Gojo, J. ; Kool, M. (Last author)DKFZ* ; Hovestadt, V. ; Filbin, M. G.

2025
Nature Research London

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s43018-025-00964-9

Abstract: 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.

Note: #LA:B062# / 2025 Jun;6(6):1035-1055

---

Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. KKE Neuropathologie (B300)
4. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---