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研究探寻神经母细胞瘤的发育起源
2021-03-28 13:45

德国海德堡霍普儿童癌症中心(KiTZ)Frank Westermann 研究组取得最新进展。他们利用单细胞转录组学分析为神经母细胞瘤的发育起源提供了见解。2021年3月25日出版的《自然-遗传学》杂志发表了这一成果。

他们研究了神经母细胞瘤和正常人类发育的肾上腺在胚胎和胎儿发育的各个阶段的单细胞转录组。他们定义了从雪旺细胞前体到中间状态再到嗜铬细胞或嗜铬细胞的正常分化轨迹,并表明成人神经细胞瘤在转录上类似于正常胎儿肾上腺成神经细胞。

重要的是,具有不同临床表型的神经母细胞瘤沿正常的神经母细胞分化轨迹时间状态相匹配,并且分化程度与临床预后相对应。他们的工作强调了致癌性MYCN和TFAP2B缺失在阻止分化中的作用,并可能为设计克服分化障碍的治疗性干预措施提供基础。

据介绍,神经母细胞瘤是发育中的交感神经系统的儿科肿瘤。但是,神经母细胞瘤的细胞起源尚未确定。

附:英文原文

Title: Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma

Author: Selina Jansky, Ashwini Kumar Sharma, Verena Krber, Andrs Quintero, Umut H. Toprak, Elisa M. Wecht, Moritz Gartlgruber, Alessandro Greco, Elad Chomsky, Thomas G. P. Grnewald, Kai-Oliver Henrich, Amos Tanay, Carl Herrmann, Thomas Hfer, Frank Westermann

Issue&Volume: 2021-03-25

Abstract: Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma has yet to be defined. Here we studied the single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We defined normal differentiation trajectories from Schwann cell precursors over intermediate states to neuroblasts or chromaffin cells and showed that neuroblastomas transcriptionally resemble normal fetal adrenal neuroblasts. Importantly, neuroblastomas with varying clinical phenotypes matched different temporal states along normal neuroblast differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis. Our work highlights the roles of oncogenic MYCN and loss of TFAP2B in blocking differentiation and may provide the basis for designing therapeutic interventions to overcome differentiation blocks. A single-cell transcriptomic analysis of neuroblastomas and healthy adrenal glands defines cell types and lineage trajectories during different developmental stages. Comparisons with the transcriptomes of neuroblastoma cells show that their transcriptomes most closely resemble those of developing neuroblasts of the adrenal gland.

DOI: 10.1038/s41588-021-00806-1

Source: https://www.nature.com/articles/s41588-021-00806-1

 

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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