ArticleNature2013
Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 691 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
691 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,286 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- Single-cell RNA sequencing analysis of bone cancer pain model induced by Lewis lung cancer cells in male mice.Annals of medicine · 2026Article
- Interpretable machine learning enables de novo mapping of cell type-specific RNA splicing regulation from scRNA-seq data.Nature communications · 2026Article
- Concerted changes in the pediatric single-cell intestinal ecosystem before and after anti-TNF blockade.eLife · 2026Article
- DEAPLOG: Differential Expression Analysis and Pseudo-Temporal Locating and Ordering of Genes in Single-Cell Transcriptomic Data.Interdisciplinary sciences, computational life sciences · 2026Article
- The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tools and tactics for studying alternative splicing.Nature reviews. Genetics · 2026Review
- Bacterial surface display enables lysis-independent joint host-pathogen single-cell profiling.bioRxiv : the preprint server for biology · 2026Article
- Interpretable deep generative ensemble learning for single-cell omics with Hydra.Molecular systems biology · 2026Article
- Heritable single-cell gene expression states shape functional variability in innate immune responses.bioRxiv : the preprint server for biology · 2026Article
- Decoding Immune Regulation: From Genetic Variation to Mechanism Through Single-Cell Genomics.Immune network · 2026Review
- Identifying Single-Cell Expression Quantitative Trait Loci Using a Bootstrap Penalized Hurdle Model.Genes · 2026Article
- Network clustering algorithms and preprocessing pipelines for robust cell type identification in single-cell RNA sequencing data.Scientific reports · 2026Article
- Coordinated alternative splicing decisions via stepwise exon definition.Nucleic acids research · 2026Article
- Proteoform profiling of endogenous single cells from rat hippocampus at scale.Nature biotechnology · 2026Article
- Heterogeneous NF-κB activation and enhancer features shape transcription in Drosophila immunity.Biophysical journal · 2026Article
- Epstein-Barr Virus Infection at Single-Cell Resolution.Journal of medical virology · 2026Review
- Spatial microenvironments tune immune response dynamics in the Drosophila larval fat body.PLoS genetics · 2026Article
- Advances in scCUT&Tag and computational analysis for single-cell gene regulatory element mapping.Briefings in bioinformatics · 2026Review
631 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Recent molecular studies have shown that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels and phenotypic output, with important functional consequences. Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs or proteins simultaneously, because genomic profiling methods could not be applied to single cells until very recently. Here we use single-cell RNA sequencing to investigate heterogeneity in the response of mouse bone-marrow-derived dendritic cells (BMDCs) to lipopolysaccharide. We find extensive, and previously unobserved, bimodal variation in messenger RNA abundance and splicing patterns, which we validate by RNA-fluorescence in situ hybridization for select transcripts. In particular, hundreds of key immune genes are bimodally expressed across cells, surprisingly even for genes that are very highly expressed at the population average. Moreover, splicing patterns demonstrate previously unobserved levels of heterogeneity between cells. Some of the observed bimodality can be attributed to closely related, yet distinct, known maturity states of BMDCs; other portions reflect differences in the usage of key regulatory circuits. For example, we identify a module of 137 highly variable, yet co-regulated, antiviral response genes. Using cells from knockout mice, we show that variability in this module may be propagated through an interferon feedback circuit, involving the transcriptional regulators Stat2 and Irf7. Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.