影像学和多组学数据集的融合定义了 ATRT-SHH 亚组不同的神经前体细胞起源。

Imaging and multi-omics datasets converge to define different neural progenitor origins for ATRT-SHH subgroups.

机构信息

INSERM U830, Laboratory of Translational Research In Pediatric Oncology, PSL Research University, SIREDO Oncology center, Institut Curie Research Center, Paris, France.

INSERM U900, Bioinformatics, Biostatistics, Epidemiology and Computational Systems Unit, Institut Curie, Mines Paris Tech, PSL Research University, Institut Curie Research Center, Paris, France.

出版信息

Nat Commun. 2023 Oct 20;14(1):6669. doi: 10.1038/s41467-023-42371-7.

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::Smarcb1 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.

非典型畸胎样横纹肌样肿瘤（ATRT）分为 MYC、TYR 和 SHH 亚组，提示其具有不同的起源谱系。在这里，我们研究了人类 ATRT 诊断时的影像学表现，以及 Rosa26-Cre::Smarcb1 模型中脑肿瘤的精确解剖起源。这项跨物种分析表明，MYC 肿瘤起源于脑外。此外，我们清楚地区分了起源于小脑前叶（CAL）的 SHH ATRT 和起源于基底节（BG）和脑室（IV）区域的 SHH ATRT。分子特征表明，CAL SHH ATRT 的起源是中脑-后脑边界，而 BG/IV SHH ATRT 的起源是神经节隆起。对 SHH ATRT 的单细胞 RNA 测序支持这些假说。轨迹分析表明，SMARCB1 缺失诱导了一种去分化过程，该过程由神经元程序的抑制剂介导，如 REST、ID 和 NOTCH 通路。