Science: new technologies witness the "real face" of cancer cells in front of drugs

SCI plex, a new cell response screening technology reported in science, can collect different cells and show the changes of single cells when being treated with drugs Compared with the current typical high-throughput chemical screening (HTS), it is not limited to rough readings (such as changes in cell survival rate, proliferation or cell shape), or specific molecular discovery, This provides powerful data for exploring drug mechanism DOI: 10.1126/science.aax6234 By combining the nuclear labeling technique with the single cell combinatorial index (SCI RNA SEQ), the analysis can be done in an economical and effective way at the single cell resolution This technique is called "SCI plex" SCI plex: cell hash and multi sample SCI RNA SEQ binding detection The results showed that the hash oligonucleotides could stably label the nucleus in a way compatible with SCI RNA SEQ, which promoted the identification of the majority of interspecies (95.5%) and intraspecies dual States, and was not easy to detect To evaluate SCI plex and HTS, the researchers applied them to the screening of three cancer cell lines of K562 (leukemia), A549 (lung cancer) and MCF7 (breast cancer), treated them with 188 drugs for cancer, HIV and autoimmune diseases, and labeled them with small single stranded DNA In total, the researchers described 650000 single cell transcriptional sequences from about 5000 independent samples, distinguishing between generic and cell line specific responses to each compound SCI plex can perform global transcription analysis for thousands of chemical disturbances in one experiment Uniform manifold approximation projection (umap) projects most of the cells of each cell line into a central cluster, next to which are smaller clusters In the experiment, only 52 compounds (27%) decreased the survival rate of cancer cells by 50% or more Among them, histone deacetylase (HDAC) inhibitors of cancer drugs have the most significant response to the compounds treated by cells Researchers have studied the action mode of HDAC inhibitors more deeply, and found that the change of gene regulation is consistent with that of these inhibitors to prevent the increase of cancer cells by preventing the acquisition of energy Co transcriptional response of HDAC inhibitors indicates a lack of acetyl coa With the increase of chromatin binding acetate, these transcriptional responses indicated that the acetyl CoA reserve decreased in HDAC inhibited cells In general, SCI plex results show that it can be scaled to thousands of samples to target a variety of biochemical pathways, catalysts, regulators and modes of action "This study can help medical researchers understand how certain drugs work, how cell stages affect efficacy, and why certain drugs work only on specific cells," said Trapnell, senior author