小柯机器人

意大利热那亚大学Paolo Malatesta课题组利用基因条形码揭示胶质母细胞瘤进展中的早期克隆消失。2023年8月3日，国际知名学术期刊《癌细胞》发表了这一成果。

他们将PDGFB和基因条形码转移到小鼠大脑中，以启动胶质母细胞瘤的形成，并从最早的可能阶段直接追踪胶质母细胞瘤的进化。出乎意料的是，他们观察到克隆灭绝事件的高发生率和克隆大小的逐渐分化，甚至在获得恶性表型之后。计算模型表明，这些动态是基于克隆的细胞-细胞竞争的结果。通过大量和单细胞转录组分析，再加上谱系追踪，他们发现Myc转录靶点与克隆大小失衡具有最强的相关性。

此外，他们发现Myc表达的下调足以驱动颅内移植胶质瘤的竞争动态。他们的研究结果为胶质母细胞瘤的进化提供了传统回顾性方法无法获得的见解，突出了在该领域结合克隆追踪和转录组学分析的潜力。

据了解，胶质母细胞瘤早期的进展仍然知之甚少。

附：英文原文

Title: Early clonal extinction in glioblastoma progression revealed by genetic barcoding

Author: Davide Ceresa, Francesco Alessandrini, Sara Lucchini, Daniela Marubbi, Francesca Piaggio, Jorge Miguel Mena Vera, Isabella Ceccherini, Daniele Reverberi, Irene Appolloni, Paolo Malatesta

Issue&Volume: 2023-08-03

Abstract: Glioblastoma progression in its early stages remains poorly understood. Here, we transfer PDGFB and genetic barcodes in mouse brain to initiate gliomagenesis and enable direct tracing of glioblastoma evolution from its earliest possible stage. Unexpectedly, we observe a high incidence of clonal extinction events and progressive divergence in clonal sizes, even after the acquisition of malignant phenotype. Computational modeling suggests these dynamics result from clonal-based cell-cell competition. Through bulk and single-cell transcriptome analyses, coupled with lineage tracing, we reveal that Myc transcriptional targets have the strongest correlation with clonal size imbalances. Moreover, we show that the downregulation of Myc expression is sufficient to drive competitive dynamics in intracranially transplanted gliomas. Our findings provide insights into glioblastoma evolution that are inaccessible using conventional retrospective approaches, highlighting the potential of combining clonal tracing and transcriptomic analyses in this field.

DOI: 10.1016/j.ccell.2023.07.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00241-6

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx