Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong S.A.R., China.
Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong S.A.R., China.
Sci Adv. 2023 Jan 4;9(1):eabp8901. doi: 10.1126/sciadv.abp8901.
Single-cell multi-omics can provide a unique perspective on tumor cellular heterogeneity. Most previous single-cell whole-genome RNA sequencing (scWGS-RNA-seq) methods demonstrate utility with intact cells from fresh samples. Among them, many are not applicable to frozen samples that cannot produce intact single-cell suspensions. We have developed scONE-seq, a versatile scWGS-RNA-seq method that amplifies single-cell DNA and RNA without separating them from each other and hence is compatible with frozen biobanked samples. We benchmarked scONE-seq against existing methods using fresh and frozen samples to demonstrate its performance in various aspects. We identified a unique transcriptionally normal-like tumor clone by analyzing a 2-year frozen astrocytoma sample, demonstrating that performing single-cell multi-omics interrogation on biobanked tissue by scONE-seq could enable previously unidentified discoveries in tumor biology.
单细胞多组学可以提供一个独特的视角来研究肿瘤细胞异质性。大多数之前的单细胞全基因组 RNA 测序（scWGS-RNA-seq）方法都证明了它们在从新鲜样本中获得完整细胞时的有效性。其中，许多方法不适用于无法产生完整单细胞悬液的冷冻样本。我们开发了 scONE-seq，这是一种通用的 scWGS-RNA-seq 方法，它可以扩增单细胞 DNA 和 RNA，而无需将它们彼此分离，因此与冷冻生物样本库样本兼容。我们使用新鲜和冷冻样本对 scONE-seq 进行了基准测试，以证明其在各个方面的性能。我们通过分析一个 2 年的冷冻星形细胞瘤样本，鉴定出一个独特的转录正常样肿瘤克隆，这表明通过 scONE-seq 对生物样本库组织进行单细胞多组学研究可以使肿瘤生物学中的以前未被识别的发现成为可能。
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