Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.

IF 16.4 1区医学 Q1 CLINICAL NEUROLOGY

Neuro-oncology Pub Date : 2025-06-24 DOI:10.1093/neuonc/noaf129

Shoma Tsubota, Daniel R Carter, Janith A Seneviratne, Haruka Hirose, Teppei Shimamura, Yukie Kashima, Yutaka Suzuki, Koji Tsuda, Glenn M Marshall, Kenji Kadomatsu

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引用次数: 0

Abstract

Background: Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer.

Methods: Here, we analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma. Single-cell transcriptomic analysis of ganglion tissues from Th-MYCN mice was conducted to elucidate the cellular and molecular underpinnings.

Results: Trajectory analysis of pre-cancerous neuroblasts revealed a distinct subtype we designated as "uncommitted" cells, characterized by the expression of neuronal genes, indicative of a semi-differentiated state. Samples with predicted failed tumorigenesis had a greater proportion of these uncommitted cells, hinting at their association with spontaneous regression. In clinical specimens, heightened uncommitted gene expression corresponded with favorable neuroblastomas and an improved prognosis.

Conclusion: Collectively, the identification of this novel neuroblastoma-related cell subtype and its transcriptomic signature not only enhances our understanding of spontaneous regression mechanisms but also holds potential for therapeutic advancements in treating neuroblastomas.

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轨迹分析显示，在mycn驱动的神经母细胞瘤发展过程中，神经母细胞状态不稳定。

背景：了解决定癌前病变自发消退的因素对推进癌症预防至关重要。神经母细胞瘤是一种儿童癌症，比其他类型的癌症更容易自发消退。方法：在这里，我们使用Th-MYCN小鼠（一种与人类神经母细胞瘤非常相似的动物模型）分析癌前神经母细胞自发消退的转录组学特征。对Th-MYCN小鼠神经节组织进行单细胞转录组学分析，以阐明细胞和分子基础。结果：癌前神经母细胞的轨迹分析揭示了一种独特的亚型，我们将其命名为“未分化”细胞，其特征是神经元基因的表达，表明半分化状态。预测肿瘤发生失败的样本中，这些未分化细胞的比例更大，暗示它们与自发退化有关。在临床标本中，增高的未确定基因表达与神经母细胞瘤的良好预后相对应。结论：总的来说，这种新的神经母细胞瘤相关细胞亚型及其转录组特征的鉴定不仅增强了我们对自发消退机制的理解，而且在治疗神经母细胞瘤方面具有潜在的治疗进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuro-oncology 医学-临床神经学

CiteScore

27.20

自引率

6.30%

发文量

1434

审稿时长

3-8 weeks

期刊介绍： Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.