{"doi":"10.1038/s41586-019-1369-y","title":"scSLAM-seq reveals core features of transcription dynamics in single cells","abstract":"Single-cell RNA sequencing (scRNA-seq) has highlighted the important role of intercellular heterogeneity in phenotype variability in both health and disease<sup>1</sup>. However, current scRNA-seq approaches provide only a snapshot of gene expression and convey little information on the true temporal dynamics and stochastic nature of transcription. A further key limitation of scRNA-seq analysis is that the RNA profile of each individual cell can be analysed only once. Here we introduce single-cell, thiol-(SH)-linked alkylation of RNA for metabolic labelling sequencing (scSLAM-seq), which integrates metabolic RNA labelling<sup>2</sup>, biochemical nucleoside conversion<sup>3</sup> and scRNA-seq to record transcriptional activity directly by differentiating between new and old RNA for thousands of genes per single cell. We use scSLAM-seq to study the onset of infection with lytic cytomegalovirus in single mouse fibroblasts. The cell-cycle state and dose of infection deduced from old RNA enable dose-response analysis based on new RNA. scSLAM-seq thereby both visualizes and explains differences in transcriptional activity at the single-cell level. Furthermore, it depicts 'on-off' switches and transcriptional burst kinetics in host gene expression with extensive gene-specific differences that correlate with promoter-intrinsic features (TBP-TATA-box interactions and DNA methylation). Thus, gene-specific, and not cell-specific, features explain the heterogeneity in transcriptomes between individual cells and the transcriptional response to perturbations.","journal":"Nature","year":2019,"id":2878,"datarank":0.8251887315817092,"base_score":5.501258210544727,"endowment":5.501258210544727,"self_citation_contribution":0.8251887315817092,"citation_network_contribution":0.0,"self_endowment_contribution":0.8251887315817092,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":244,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.076,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2019-07-10","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":32233,"name":"Marisa A. P. Baptista","orcid":null,"position":1,"is_corresponding":false},{"id":32234,"name":"Tobias Krammer","orcid":"0000-0002-7638-9476","position":2,"is_corresponding":false},{"id":32235,"name":"Thomas Hennig","orcid":"0000-0002-7788-1681","position":3,"is_corresponding":false},{"id":2914,"name":"Marius Lange","orcid":"0000-0002-4846-1266","position":4,"is_corresponding":false},{"id":32236,"name":"Panagiota Arampatzi","orcid":"0000-0001-7925-8984","position":5,"is_corresponding":false},{"id":32237,"name":"Christopher S. Jürges","orcid":null,"position":6,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":7,"is_corresponding":false},{"id":65617,"name":"Jonathan D. Rohrer","orcid":"0000-0002-6155-8417","position":8,"is_corresponding":false},{"id":32238,"name":"Lars Dölken","orcid":"0000-0002-4651-3544","position":9,"is_corresponding":false},{"id":32239,"name":"Christopher Jürges","orcid":null,"position":10,"is_corresponding":false},{"id":28524,"name":"Antoine‐Emmanuel Saliba","orcid":"0000-0001-8539-2784","position":11,"is_corresponding":false},{"id":32232,"name":"Florian Erhard","orcid":"0000-0002-3574-6983","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}