Single-cell chemical transcriptomics Single-cell transcriptomic technologies have emerged as powerful tools to explore cellular heterogeneity at the resolution of individual cells. Srivatsan et al. now add another layer of information and complexity by combining single-cell transcriptomics with oligo hashing and small molecule screening in a method called sci-Plex. Because screening many chemical compounds requires the ability to profile many cells, and because screens perturb cells in many different ways, the authors demonstrate the effects of 188 compounds in three cancer lines. The sci-Plex method can capture gene expression profiles from thousands of experimental conditions in a single experiment. Science, this issue p. 45 A technique termed sci-Plex can screen the effects of multiple chemical treatments on gene expression in single cells. High-throughput chemical screens typically use coarse assays such as cell survival, limiting what can be learned about mechanisms of action, off-target effects, and heterogeneous responses. Here, we introduce “sci-Plex,” which uses “nuclear hashing” to quantify global transcriptional responses to thousands of independent perturbations at single-cell resolution. As a proof of concept, we applied sci-Plex to screen three cancer cell lines exposed to 188 compounds. In total, we profiled ~650,000 single-cell transcriptomes across ~5000 independent samples in one experiment. Our results reveal substantial intercellular heterogeneity in response to specific compounds, commonalities in response to families of compounds, and insight into differential properties within families. In particular, our results with histone deacetylase inhibitors support the view that chromatin acts as an important reservoir of acetate in cancer cells.

中文翻译：

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单细胞分辨率下的大规模多重化学转录组学

单细胞化学转录组学 单细胞转录组学技术已成为在单个细胞分辨率下探索细胞异质性的有力工具。斯里瓦桑等人。现在通过在一种称为 sci-Plex 的方法中将单细胞转录组学与寡核苷酸哈希和小分子筛选相结合，增加了另一层信息和复杂性。因为筛选许多化合物需要分析许多细胞的能力，并且因为筛选干扰细胞的方式很多，所以作者证明了 188 种化合物对三种癌细胞系的影响。sci-Plex 方法可以在单个实验中从数千个实验条件中捕获基因表达谱。科学，这个问题 p。45 一种称为 sci-Plex 的技术可以筛选多种化学处理对单个细胞中基因表达的影响。高通量化学筛选通常使用粗略的分析，如细胞存活，限制了可以了解的关于作用机制、脱靶效应和异质反应的内容。在这里，我们介绍了“sci-Plex”，它使用“核散列”来量化对单细胞分辨率下数千个独立扰动的全局转录反应。作为概念证明，我们应用 sci-Plex 来筛选暴露于 188 种化合物的三种癌细胞系。在一项实验中，我们总共分析了约 5000 个独立样本中的约 650,000 个单细胞转录组。我们的研究结果揭示了对特定化合物反应的大量细胞间异质性、对化合物家族反应的共性，以及对家族内不同特性的洞察。特别是，