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科学家发现小儿脑瘤的根源是发育停滞
作者:小柯机器人 发布时间:2019/11/26 17:25:38

加拿大犹太总医院戴维斯夫人医学研究所Claudia L. Kleinman研究组最新研究发现,小儿脑瘤的根源是发育停滞。11月25日,国际学术期刊《自然—遗传学》在线发表了这一成果。

为了确定哪个发育阶段更容易受到损伤,研究人员从两个主要的肿瘤部位-胚胎脑桥和前脑中描绘了一个超过65,000个细胞的单细胞转录组图谱。研究人员发现了191个不同细胞群体的特征,确定了区域细胞多样性和分化动力学。

通过将大量肿瘤转录组投射到该数据集,研究人员发现WNT亚型髓母细胞瘤与菱形唇来源的苔藓纤维神经元谱系相匹配,多层玫瑰花结样胚胎瘤完全涵盖了一种神经元谱系,而2a / b组非典型类畸胎瘤/类瘤样瘤可能起源于神经外胚层。

此外,单细胞肿瘤图谱揭示了高度清晰的细胞层次,同时反映了相应正常谱系的转录进程。该研究表明特定神经祖细胞的分化受损是这些小儿癌症的常见机制,并为将来的建模和治疗提供了合理的机制。

附:英文原文

Title: Stalled developmental programs at the root of pediatric brain tumors

Author: Selin Jessa, Alexis Blanchet-Cohen, Brian Krug, Maria Vladoiu, Marie Coutelier, Damien Faury, Brice Poreau, Nicolas De Jay, Steven Hbert, Jean Monlong, W. Todd Farmer, Laura K. Donovan, Yixing Hu, Melissa K. McConechy, Florence M. G. Cavalli, Leonie G. Mikael, Benjamin Ellezam, Maxime Richer, Andra Allaire, Alexander G. Weil, Jeffrey Atkinson, Jean-Pierre Farmer, Roy W. R. Dudley, Valerie Larouche, Louis Crevier, Steffen Albrecht, Mariella G. Filbin, Herv Sartelet, Pierre-Eric Lutz, Corina Nagy, Gustavo Turecki, Santiago Costantino, Peter B. Dirks, Keith K. Murai, Guillaume Bourque, Jiannis Ragoussis, Livia Garzia, Michael D. Taylor, Nada Jabado, Claudia L. Kleinman

Issue&Volume: 2019-11-25

Abstract: Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.

DOI: 10.1038/s41588-019-0531-7

Source: https://www.nature.com/articles/s41588-019-0531-7

期刊信息

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:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex