Mesenchymal-like (MES-like) glioblastoma cell state胶质母细胞瘤间充质样（MES 样）细胞状态

Research question研究问题

• What is the mesenchymal-like (MES-like) state in glioblastoma?胶质母细胞瘤的间充质样（MES 样）状态是什么？
• What drives glioblastoma cells toward a MES-like state?是什么驱动 GBM 细胞向 MES 样状态转变？
• Can any model currently simulate how MES-like cells respond to therapy?目前有模型能模拟 MES 样细胞对治疗的反应吗？

Current understanding当前认识

MES-like is one of four recurrent malignant cell states in glioblastoma described by Neftel et al. (2019). Studies in the library link transitions toward MES-like or mesenchymal programs to immune interactions, BRD2/NF-κB signalling and recurrence after therapy; no model in the library has been shown to simulate MES-like therapy response accurately.MES 样是 Neftel 等（2019）描述的胶质母细胞瘤四种反复出现的恶性细胞状态之一。文献库中的研究将向 MES 样/间充质程序的转变与免疫相互作用、BRD2/NF-κB 信号及治疗后复发相关联；尚无文献库中的模型被证明能准确模拟 MES 样细胞的治疗反应。

Neftel et al. combined single-cell RNA-seq of 28 tumors with bulk data from 401 TCGA specimens and lineage tracing, and found that malignant GBM cells exist in four main states — NPC-like, OPC-like, AC-like and MES-like — that are influenced by the microenvironment and show plasticity. State frequencies are shaped by CDK4, EGFR and PDGFRA amplifications and NF1 mutations, each favouring a defined state (NF1 alterations with MES-like).Neftel 等结合 28 例肿瘤的单细胞 RNA 测序、401 例 TCGA 样本的批量数据及谱系示踪，发现 GBM 恶性细胞主要处于四种状态——NPC 样、OPC 样、AC 样与 MES 样——受微环境影响并具有可塑性。各状态比例受 CDK4、EGFR、PDGFRA 扩增及 NF1 突变影响，各自偏向特定状态（NF1 改变对应 MES 样）。 VC0059

Transitions toward MES-like states have been linked to interactions between cancer cells and immune cells, and to BRD2: in patient-derived xenograft models, PTEN loss recruited BRD2 to MES gene promoters, and genetic ablation of BRD2 bromodomains reversed MES transition and increased radiation sensitivity.向 MES 样状态的转变已被关联到癌细胞与免疫细胞的相互作用，以及 BRD2：在患者来源异种移植模型中，PTEN 缺失使 BRD2 被招募至 MES 基因启动子，基因敲除 BRD2 溴结构域可逆转 MES 转变并提高放射敏感性。 VC0066 VC0095

In 86 patient-matched primary–recurrent GBM pairs, recurrent tumors were characterised by a shift to a mesenchymal phenotype mediated by AP-1. This is an observation at recurrence and does not by itself show whether therapy induces or selects the state.在 86 对患者配对的原发-复发 GBM 中，复发肿瘤表现为向间充质表型转变，并由 AP-1 介导。这是复发时的观察结果，本身不能区分该状态是由治疗诱导还是被治疗筛选。 VC0069

Spatially, cell states are organised in local environments and layers that appear to be driven by hypoxia; GBmap reports hypoxia-dependent niches associated with poor prognosis.在空间上，细胞状态组织为局部环境与分层结构，缺氧似乎是驱动因素；GBmap 报告缺氧依赖的生态位与不良预后相关。 VC0061 VC0060 VC0094

Modelling status: scFOCAL links GBM cell states to LINCS L1000 drug signatures to predict state-specific sensitivity and resistance, with in vitro, ex vivo and in vivo validation in the paper. However, no model in the library has been shown to accurately simulate how MES-like cells respond to radiotherapy or chemotherapy, and general benchmarks find that deep perturbation models do not yet reliably beat simple linear baselines.建模现状：scFOCAL 将 GBM 细胞状态与 LINCS L1000 药物特征谱关联，以预测状态特异的敏感与耐药，论文中有体外、离体和体内验证。但文献库中尚无模型被证明能准确模拟 MES 样细胞对放疗或化疗的反应；通用基准显示深度扰动模型尚不能稳定超越简单线性基线。 VC0132 VC0048 VC0049

Evidence map证据图谱

Primary studies & datasets原始研究与数据集

• VC0059 An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. — Neftel C et al., Cell, 2019
• VC0066 Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. — Hara T et al., Cancer cell, 2025
• VC0095 BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma. — Vadla R et al., Neuro-oncology, 2025
• VC0069 A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets. — Wang L, Jung J, Babikir H, Shamardani K, Jain S, Feng X, Gupta N, Rosi S, Chang S, Raleigh D, Solomon D, Phillips JJ, Diaz AA., Nature cancer, 2022
• VC0061 Integrative spatial analysis reveals a multi-layered organization of glioblastoma. — Greenwald AC et al., Cell, 2024
• VC0060 Charting the single-cell and spatial landscape of IDH-wild-type glioblastoma with GBmap. — Ruiz-Moreno C et al., Neuro-oncology, 2025
• VC0094 Hypoxia coordinates the spatial landscape of myeloid cells within glioblastoma to affect survival. — Haley MJ et al., Science advances, 2024
• VC0092 · preprint · 预印本 Mapping the spatial architecture of glioblastoma from core to edge delineates niche-specific tumor cell states and intercellular interactions — Khan SM et al., bioRxiv, 2025

Related models & tools相关模型与工具

• VC0132 Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations — Suter et al., Nature Communications, 2026
• VC0072 A method for in silico exploration of potential glioblastoma multiforme attractors using single-cell RNA sequencing. — Vieira Junior MG, de Almeida Côrtes AM, Gonçalves Carneiro FR, Carels N, Silva FABD., Scientific reports, 2024
• VC0001 How to build the virtual cell with artificial intelligence: Priorities and opportunities. — Bunne C et al., Cell, 2024

Perturbation & validation evidence扰动与验证证据

• VC0070 In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma. — Liu SJ et al., Genome biology, 2024
• VC0048 Deep-learning-based gene perturbation effect prediction does not yet outperform simple linear baselines. — Ahlmann-Eltze C, Huber W, Anders S., Nature methods, 2025
• VC0049 Benchmarking foundation cell models for post-perturbation RNA-seq prediction. — Csendes G, Sanz G, Szalay KZ, Szalai B., BMC genomics, 2025

14 library items cited on this page; 1 are preprints (not peer reviewed).本页引用文献库条目 14 条，其中预印本（未经同行评审）1 条。

What remains uncertain尚不确定之处

“MES-like” (Neftel), “mesenchymal phenotype” at recurrence and spatially defined niche states are related but not identical definitions; results may not transfer between them.Neftel 的“MES 样”、复发时的“间充质表型”与空间定义的生态位状态彼此相关但并不等同，结论未必可互相迁移。 VC0059 VC0069 VC0092 · preprint · 预印本

Whether therapy induces MES-like transitions or selects pre-existing MES-like cells in patients is not resolved by the cited work.在患者体内，治疗是诱导 MES 样转变还是筛选已有的 MES 样细胞，现有引用文献尚未解决。 VC0069

Mechanistic findings (e.g. BRD2) come from xenograft and cell models; spatial core-to-edge states are from a preprint.机制性结论（如 BRD2）来自异种移植与细胞模型；从肿瘤核心到边缘的空间状态来自预印本。 VC0095 VC0092 · preprint · 预印本

No prospective clinical validation of MES-targeted strategies or MES-state models was found in the library.文献库中未发现针对 MES 的策略或 MES 状态模型的前瞻性临床验证。

Related questions相关问题

• Does glioblastoma change cell state after radiotherapy and chemotherapy?放化疗后胶质母细胞瘤的细胞状态会改变吗？
• Is GBM recurrence driven by new mutations or by phenotype switching?GBM 复发由新突变驱动还是由表型转换驱动？
• What are NPC-like and OPC-like cells in glioblastoma?GBM 中的 NPC 样与 OPC 样细胞是什么？
• Do glioma cells follow a neurodevelopmental hierarchy?胶质瘤细胞是否遵循神经发育层级？
• What single-cell and spatial datasets exist for glioblastoma?胶质母细胞瘤有哪些单细胞与空间数据集？
• What is GBmap?GBmap 是什么？
• What is an AI virtual cell model?什么是 AI 虚拟细胞模型？
• Which virtual cell models have been applied to glioblastoma?哪些虚拟细胞模型已应用于胶质母细胞瘤？
• Do GBM cell-state calls replicate on an independent platform, and does the state structure go beyond the signature genes?GBM 细胞状态判定能否在独立平台上复现，状态结构是否超出特征基因本身？
• How much does a trivial baseline recover?简单基线能还原多少？