Massively multiplex chemical transcriptomics at single-cell resolution

By S. Srivatsan, J. McFaline-Figueroa, V. Ramani, Lauren M. Saunders, Junyue Cao, Jonathan S. Packer, Hannah A. Pliner, Dana L. Jackson, R. Daza, Lena Christiansen and 4 more. Science, 2019

364 citations recorded by the source corpus.

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.

Subfields: Biophysics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/64c13037fea56c2c15ed18994be3b593d9c5beca

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Citations in the corpus

Predicting cellular responses to complex perturbations in high‐throughput screens (2023, methodology): “Recently, novel technologies have been developed extending these measurements to high-throughput screens (HTSs), which measure response to thousands of independent perturbations (Norman et al , 2019; Srivatsan et al , 2020).”