文章：

多层级玫瑰花结胚胎性肿瘤的细胞层级结构由致癌性微小RNA及受体-配体相互作用共同塑造

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

原文发布日期: 2025-05-26 

英文摘要:

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.

摘要翻译：

具有多层菊形团的胚胎性肿瘤（ETMR）是一种预后极差的儿童脑肿瘤。尽管在多数ETMR病例中可观察到19号染色体microRNA簇（C19MC）的特征性改变，但C19MC激活的生物学效应及其复杂的肿瘤细胞结构仍缺乏深入研究。本研究通过单细胞转录组学和多重空间成像技术分析了11例患者来源的ETMR样本，揭示了一个空间分布明确的细胞层级结构——包括高增殖性的神经干细胞样细胞和分化程度更高的神经元样细胞。全基因组microRNA-mRNA结合分析显示，C19MC主要在干细胞样细胞中表达，并通过调控转录网络主导干性维持和谱系分化。对恶性细胞类型间受体-配体相互作用的系统分析表明，成纤维细胞生长因子受体和Notch信号通路可作为致癌通路靶点，这一发现在临床前模型及一例ETMR患者治疗中已获得验证。本研究为ETMR的病理生物学机制提供了重要见解，并为开发更有效的靶向治疗奠定了理论基础。

原文链接:

https://www.nature.com/articles/s43018-025-00964-9