Single-cell sequencing has emerged as an indispensable technology to dissect cellular heterogeneity but never been applied to the simultaneous analysis of glycan and RNA. Using oligonucleotide-labeled lectins, we first established lectin-based glycan profiling of single cells by sequencing (scGlycan-seq). We then combined the scGlycan-seq with single-cell transcriptome profiling (scRNA-seq) for joint analysis of glycan and RNA in single cells (scGR-seq). Using scGR-seq, we analyzed the two modalities in human induced pluripotent stem cells (hiPSCs) before and after differentiation into neural progenitor cells at the single cell resolution. The combination of RNA and glycan separated the two cell types clearer than either one of them. Furthermore, integrative analysis of glycan and RNA modalities in single cells found known and novel lectins that were specific to hiPSCs and coordinated with neural differentiation. Taken together, we demonstrate that scGR-seq can reveal the cellular heterogeneity and biological roles of glycans across multicellular systems.

中文翻译：

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整合分析单细胞中的聚糖和RNA

单细胞测序已成为一种分析细胞异质性的必不可少的技术，但从未应用于聚糖和RNA的同时分析。使用寡核苷酸标记的凝集素，我们首先通过测序（scGlycan-seq）建立了单细胞的基于凝集素的聚糖谱。然后，我们将scGlycan-seq与单细胞转录组分析（scRNA-seq）结合起来，对单细胞（scGR-seq）中的聚糖和RNA进行联合分析。使用scGR-seq，我们分析了人类诱导的多能干细胞（hiPSC）在以单细胞分辨率分化为神经祖细胞之前和之后的两种模式。RNA和聚糖的组合使两种细胞类型比其中一种更清晰。此外，单个细胞中的聚糖和RNA形态的综合分析发现了已知和新颖的凝集素，这些凝集素对hiPSC具有特异性并与神经分化相协调。综上所述，我们证明了scGR-seq可以揭示跨多细胞系统的聚糖的细胞异质性和生物学作用。