Single-Cell Sequencing of Diffuse Midline Glioma Reveals That CTHRC1 Promotes Tumor Malignant Progression via the Wnt/β-Catenin/MMP2 Signaling Pathway.

Abstract

Despite the continuous advancement of neurosurgical techniques and the accelerated pace of drug development, the prognosis of diffuse midline glioma (DMG) remains unsatisfactory. Reports on the cellular atlas and biological characteristics of DMG remain relatively scarce. With the rapid development of biotechnology, especially single-cell transcriptome technology, people's understanding of the tumor microenvironment (TME) of DMG can be effectively enhanced. Here, we performed an integrated analysis of single-cell transcriptome profiles from 3 DMG samples collected from our center to investigate the characteristics of intratumoral heterogeneity and the TME. As a core component of DMG tumor cells, oligodendrocyte progenitor cells (OPCs) are predominantly localized in the cellular tumor (CT) region, whereas OPCs in the leading edge (LE) and microvascular proliferation (MVP) regions contribute to immune suppression. The pseudotime trajectory of monocyte-derived macrophages (MDMs) demonstrates that they infiltrate the tumor tissues via the microvascular proliferation (MVP) and leading edge (LE) regions, and then migrate toward the tumor core (CT) or pseudo-palisading cells around necrosis (PAN) regions, which is correlated with tumor immune suppression. In addition, CTHRC1 can promote the malignant progression of DMG via the Wnt/β-catenin/MMP2 signaling pathway. Together, our work provides an in-depth understanding of the microenvironment of DMG, thereby laying a framework for uncovering targeted therapeutic strategies for DMG.