Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions

被引：0

作者：

Beck, Alexander ^{[2
,3
,4
]}

Gabler-Pamer, Lisa ^{[1
,3
,5
,6
]}

Alencastro Veiga Cruzeiro, Gustavo ^{[1
,2
,3
]}

Lambo, Sander ^{[1
,2
,3
,7
,8
,9
,10
]}

Englinger, Bernhard ^{[1
,2
,11
]}

Shaw, McKenzie L. ^{[1
,2
,3
]}

Hack, Olivia A. ^{[1
,2
,3
]}

Liu, Ilon ^{[1
,2
,3
]}

Haase, Rebecca D. ^{[1
,2
,3
]}

de Biagi Jr, Carlos A. O. ^{[1
,2
,3
]}

Baumgartner, Alicia ^{[1
,2
,3
]}

Nascimento Silva, Andrezza Do ^{[1
,2
,3
]}

Klenner, Marbod ^{[4
]}

Freidel, Pia S. ^{[4
]}

Herms, Jochen ^{[4
]}

von Baumgarten, Louisa ^{[12
,13
]}

Tonn, Joerg C. ^{[12
,13
]}

Thon, Niklas ^{[12
,13
]}

Bruckner, Katharina ^{[14
]}

Madlener, Sibylle ^{[14
]}

Mayr, Lisa ^{[14
]}

Senfter, Daniel ^{[14
]}

Peyrl, Andreas ^{[14
]}

Slavc, Irene ^{[14
]}

Loetsch, Daniela ^{[6
]}

Dorfer, Christian ^{[6
]}

Geyregger, Rene ^{[15
]}

Amberg, Nicole ^{[16
]}

Haberler, Christine ^{[16
]}

Mack, Norman ^{[7
,8
,9
]}

Schwalm, Benjamin ^{[7
,8
,9
]}

Pfister, Stefan M. ^{[7
,8
,17
]}

Korshunov, Andrey ^{[9
,18
,19
]}

Baird, Lissa C. ^{[20
]}

Yang, Edward ^{[21
]}

Chi, Susan N. ^{[2
]}

Alexandrescu, Sanda ^{[22
]}

Gojo, Johannes ^{[14
]}

Kool, Marcel ^{[7
,8
,9
,23
,24
]}

Hovestadt, Volker ^{[1
,2
,3
]}

Filbin, Mariella G. ^{[1
,2
,3
]}

机构：

[1] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[2] Blood Disorders Ctr, Boston, MA 02115 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Ludwig Maximilians Univ Munchen, Ctr Neuropathol, Munich, Germany

[5] Med Univ Vienna, Dept Neurosurg, Vienna, Austria

[6] Med Univ Vienna, Comprehens Canc Ctr, Vienna, Austria

[7] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[8] German Canc Consortium DKTK, Heidelberg, Germany

[9] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

[10] BC Canc, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[11] Med Univ Vienna, Comprehens Canc Ctr, Dept Urol, Vienna, Austria

[12] Univ Munich, Univ Hosp Ludwig Maximilians, Dept Neurosurg, Munich, Germany

[13] German Canc Consortium DKTK, Partner Site Munich, Munich, Germany

[14] Med Univ Vienna, Comprehens Ctr Pediat, Vienna, Austria

[15] St Anna Childrens Canc Res Inst, Clin Cell Biol & FACS Core Unit, Vienna, Austria

[16] Med Univ Vienna, Dept Neurol, Div Neuropathol & Neurochem, Vienna, Austria

[17] Heidelberg Univ Hosp, Dept Paediat Haematol & Oncol, Heidelberg, Germany

[18] Heidelberg Univ Hosp, Dept Neuropathol, Heidelberg, Germany

[19] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[20] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA

[21] Boston Childrens Hosp, Dept Radiol, Boston, MA USA

[22] Boston Childrens Hosp, Dept Pathol, Boston, MA USA

[23] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[24] Univ Med Ctr Utrecht UMCU, Utrecht, Netherlands

来源：

NATURE CANCER | 2025年 / 6卷 / 06期

基金：

奥地利科学基金会; 美国国家卫生研究院;

关键词：

NEURAL STEM-CELLS; RNA-SEQ; NERVOUS-SYSTEM; SUBVENTRICULAR ZONE; CLUSTER C19MC; EXPRESSION; REVEALS; ROLES; NEUROGENESIS; TRAJECTORIES;

D O I：

10.1038/s43018-025-00964-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1035 / 1055

页数：45

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