Minoshima Fumi, Ozaki Haruka, Odaka Haruki, Tateno Hiroaki
Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Bioinformatics Laboratory, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
iScience. 2021 Jul 17;24(8):102882. doi: 10.1016/j.isci.2021.102882. eCollection 2021 Aug 20.
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 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 unknown 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.
单细胞测序已成为剖析细胞异质性不可或缺的技术，但从未应用于聚糖和RNA的同步分析。我们首先利用寡核苷酸标记的凝集素，通过测序建立了基于凝集素的单细胞聚糖谱分析方法（scGlycan-seq）。然后，我们将scGlycan-seq与单细胞转录组分析相结合，对单细胞中的聚糖和RNA进行联合分析（scGR-seq）。利用scGR-seq，我们在单细胞分辨率下分析了人类诱导多能干细胞（hiPSC）分化为神经祖细胞前后的这两种模式。RNA和聚糖的组合比单独的任何一种都能更清晰地区分这两种细胞类型。此外，对单细胞中聚糖和RNA模式的综合分析发现了hiPSC特有的已知和未知凝集素，它们与神经分化相关。综上所述，我们证明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。
