早期胶质母细胞瘤（GBM）的进展仍然理解有限。在这里，我们将PDGFB和遗传条形码转移到小鼠脑中以启动胶质瘤发生并实现对GBM从最早期阶段的直接追踪。出乎意料的是，我们观察到大量克隆消失事件和克隆大小逐渐分散，即使在获得恶性表型之后仍然如此。计算模型表明，这些动态是由克隆细胞间的细胞竞争所导致的。通过批量和单细胞转录组分析，结合谱系追踪，我们揭示了Myc转录靶点与克隆大小不平衡之间的最强关联。此外，我们还表明，Myc表达的下调足以推动颅内移植胶质瘤中的竞争动力学。我们的发现为无法采用传统的回顾性方法获得的GBM进化提供了洞察，并强调在这一领域中结合克隆追踪和转录组分析的潜力。 版权所有©2023作者。由Elsevier Inc.出版，版权所有。

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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.