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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1475235
This article is part of the Research Topic Unveiling Biomarkers and Mechanisms in the Tumor-Immune Nexus View all 17 articles

From Single-Cell to Spatial Transcriptomics: Decoding the Glioma Stem Cell Niche and Its Clinical Implications

Provisionally accepted
Lei Cao Lei Cao 1XU Lu XU Lu 1Xia Wang Xia Wang 1Hao Wu Hao Wu 2*Xiaye Miao Xiaye Miao 3*
  • 1 Suqian First People's Hospital, Suqian, Jiangsu Province, China
  • 2 Affiliated Huai’an Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • 3 Northern Jiangsu People's Hospital, Yangzhou University, Yangzhou, China

The final, formatted version of the article will be published soon.

    Background: Gliomas are aggressive brain tumors associated with a poor prognosis.Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature.Methods: Single-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature.Results: A distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo.This study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and and identify potential therapeutic targets, particularly 3 TUBA1C, aimed at improving patient outcomes.

    Keywords: cancer stem cells, Spatial transcriptomics, single-cell RNA sequencing, Prognostic signature, TUBA1C

    Received: 03 Aug 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Cao, Lu, Wang, Wu and Miao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hao Wu, Affiliated Huai’an Hospital of Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China
    Xiaye Miao, Northern Jiangsu People's Hospital, Yangzhou University, Yangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.