小柯机器人

2022年9月21日，美国圣犹大儿童研究医院Paul A. Northcott研究小组在《自然》杂志发表论文，揭示第3组和第4组髓母细胞瘤的统一菱唇起源。

研究人员表示，髓母细胞瘤是一种恶性的儿童小脑肿瘤，它在分子上分为生物学上不同的亚群，这表明个性化的治疗方法将是有益的。小鼠模型和跨物种基因组学已经提供了越来越多的证据，证明了离散的、亚群特定的发育起源。然而，发育中的人类组织的解剖和细胞的复杂性，特别是在菱唇生发区内，它在内化为小脑结节之前产生了所有谷氨酸神经元系，这使人们很难验证以前从小鼠研究中得出的推论。

研究人员使用了多组学方法来解析发育中的人类小脑中髓母细胞瘤亚群的起源。在人类菱唇衍生的谱系轨迹中编码的分子特征与光感受器和单极刷细胞的表达谱一致，这些表达谱在第3组和第4组髓母细胞瘤中保持不变，表明有一个趋同的基础。一个前瞻性机构队列的系统诊断-影像学审查将第3组和第4组肿瘤的推测解剖学起源定位在这些结节上。这些研究结果将临床上具有挑战性的髓母细胞瘤亚群的分子和表型特征，与它们在人类发育早期的菱唇中的统一起点联系起来。

附：英文原文

Title: Unified rhombic lip origins of group 3 and group 4 medulloblastoma

Author: Smith, Kyle S., Bihannic, Laure, Gudenas, Brian L., Haldipur, Parthiv, Tao, Ran, Gao, Qingsong, Li, Yiran, Aldinger, Kimberly A., Iskusnykh, Igor Y., Chizhikov, Victor V., Scoggins, Matthew, Zhang, Silu, Edwards, Angela, Deng, Mei, Glass, Ian A., Overman, Lynne M., Millman, Jake, Sjoboen, Alexandria H., Hadley, Jennifer, Golser, Joseph, Mankad, Kshitij, Sheppard, Heather, Onar-Thomas, Arzu, Gajjar, Amar, Robinson, Giles W., Hovestadt, Volker, Orr, Brent A., Patay, Zoltn, Millen, Kathleen J., Northcott, Paul A.

Issue&Volume: 2022-09-21

Abstract: Medulloblastoma, a malignant childhood cerebellar tumour, segregates molecularly into biologically distinct subgroups, suggesting that a personalized approach to therapy would be beneficial1. Mouse modelling and cross-species genomics have provided increasing evidence of discrete, subgroup-specific developmental origins2. However, the anatomical and cellular complexity of developing human tissues3—particularly within the rhombic lip germinal zone, which produces all glutamatergic neuronal lineages before internalization into the cerebellar nodulus—makes it difficult to validate previous inferences that were derived from studies in mice. Here we use multi-omics to resolve the origins of medulloblastoma subgroups in the developing human cerebellum. Molecular signatures encoded within a human rhombic-lip-derived lineage trajectory aligned with photoreceptor and unipolar brush cell expression profiles that are maintained in group 3 and group 4 medulloblastoma, suggesting a convergent basis. A systematic diagnostic-imaging review of a prospective institutional cohort localized the putative anatomical origins of group 3 and group 4 tumours to the nodulus. Our results connect the molecular and phenotypic features of clinically challenging medulloblastoma subgroups to their unified beginnings in the rhombic lip in the early stages of human development.

DOI: 10.1038/s41586-022-05208-9

Source: https://www.nature.com/articles/s41586-022-05208-9

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