Single-Cell and Spatial Methods for Multimodal Functional Glycan Profiling in Tissues
Basak, A.; Ortiz-Cordero, C.; Yiu, S. P. T.; Allison, S.; Sweeting, S.; Shan, F.; Tong, Y. E.; Chorghade, R.; Sosa-Guir, A.; Alakwe, S. D.; Tzouanas, C.; Zhu, B.; Gabba, A.; Yeo, Y. Y.; Wui, W.; Qiu, H.; Chang, Y.; Wang, C.; Carpenter, E. J.; Gupta, S.; Lima, G. M.; Parmelee, L.; Rock, P.; Zhang, Y.; Derda, R.; Burack, W. R.; Ma, Q.; Shalek, A. K.; Jiang, S.; Kiessling, L.
Show abstract
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.
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