Tong, Y. E. | Search bioRxiv

bioRxiv2026

Single-Cell and Spatial Methods for Multimodal Functional Glycan Profiling in Tissues

Glycans regulate multiple physiological processes, including immune recognition and cancer progression. In disease, altered glycan landscapes are interpreted by human lectins. Functional glycan-lectin interactions are difficult to profile because glycans are not genome-encoded and their changes are poorly captured by existing multimodal methods. We present two platforms, single-cell outlining and transcriptome sequencing (scGOAT-seq) and GlycoScope, which use human lectins to enable functional glycan accessibility into single-cell and spatial multiomic measurements. ScGOAT-seq quantifies lectin-accessible glycan states with gene expression, while GlycoScope enables multiplexed in situ co-detection of glycans and proteins in tissues. Applying these approaches to immune cells, we identify stimulus-specific glycan remodeling and show that distinct Siglec-ligand-defined programs stratify immune activation states not captured by traditional methods; in follicular lymphoma, GlycoScope, resolves spatial glycan programs associated with malignant B cells and localized immune microenvironments. The presented methods provide a general framework for integrating functional glycan accessibility into single-cell and spatial multiomics.

molecular biology↗

bioRxiv2023

Programs, Origins, and Niches of Immunomodulatory Myeloid Cells in Gliomas

Gliomas are incurable malignancies notable for an immunosuppressive microenvironment with abundant myeloid cells whose immunomodulatory properties remain poorly defined. Here, utilizing scRNA-seq data for 183,062 myeloid cells from 85 human tumors, we discover that nearly all glioma-associated myeloid cells express at least one of four immunomodulatory activity programs: Scavenger Immunosuppressive, C1Q Immunosuppressive, CXCR4 Inflammatory, and IL1B Inflammatory. All four programs are present in IDH1 mutant and wild-type gliomas and are expressed in macrophages, monocytes, and microglia whether of blood or resident myeloid cell origins. Integrating our scRNA-seq data with mitochondrial DNA-based lineage tracing, spatial transcriptomics, and organoid explant systems that model peripheral monocyte infiltration, we show that these programs are driven by microenvironmental cues and therapies rather than myeloid cell type, origin, or mutation status. The C1Q Immunosuppressive program is driven by routinely administered dexamethasone. The Scavenger Immunosuppressive program includes ligands with established roles in T-cell suppression, is induced in hypoxic regions, and is associated with immunotherapy resistance. Both immunosuppressive programs are less prevalent in lower-grade gliomas, which are instead enriched for the CXCR4 Inflammatory program. Our study provides a framework to understand immunomodulatory myeloid cells in glioma, and a foundation to develop more effective immunotherapies.

cancer biology↗