Widespread neuroanatomical integration and distinct electrophysiological properties of glioma- innervating neurons

• 成果类型: Article
• 署名作者: Hsieh, Annie L.; Ganesh, Sanika; Kula, Tomasz; Irshad, Madiha; Ferenczi, Emily A.; Wang, Wengang; Chen, Yi - Ching; Hu, Song - Hua; Li, Zongyu; Joshi, Shakchhi; Haigis, Marcia C.; Sabatini, Bernardo L.
• 署名单位: Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13187
• DOI: 10.1073/pnas.2417420121
• 发表日期: 2024-12-10
• 关键词: growth; cells

摘要

Gliomas are the most common malignant primary brain tumor and are often associated with severe neurological deficits and mortality. Unlike many cancers, gliomas rarely metastasize outside the brain, indicating a possible dependency on unique features of brain microenvironment. Synapses between neurons and glioma cells exist, suggesting that glioma cells rely on neuronal inputs and synaptic signaling for proliferation. Yet, the locations and properties of neurons that innervate gliomas have remained elusive. In this study, we utilized transsynaptic tracing with an EnvA- pseudotyped, glycoprotein- deleted rabies virus to specifically infect TVA and glycoprotein- expressing human glioblastoma cells in an orthotopic xenograft mouse model, allowing us to identify the neurons that form synapses onto the gliomas. Comprehensive whole- brain including diverse neuromodulatory centers and specific cortical layers, known to project to the glioma locations. Molecular profiling revealed that long- range cortical GINs are predominantly glutamatergic, and subsets express both glutamatergic and GABAergic demonstrate that while GINs share passive intrinsic properties with cortex- innervating groundwork for future investigations into how these alterations relate to the postsynaptic characteristics of glioma cells.