ArticleGenome biology2019
Combined single-cell profiling of expression and DNA methylation reveals splicing regulation and heterogeneity.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- DNA methylation aging and transcriptomic studies in horses.Nature communications · 2022Pooled it
- scASprofiler: profiling single-cell RNA splicing with a deep convolutional generative network.Briefings in bioinformatics · 2026Article
- Coordinated alternative splicing decisions via stepwise exon definition.Nucleic acids research · 2026Article
- Article
- Variations in Innate Immune Cell Subtypes Correlate with Epigenetic Clocks, Inflammaging and Health Outcomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- AEnet: a practical tool to construct the splicing-associated phenotype atlas at a single cell level.GigaScience · 2025Article
- scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood.Nature communications · 2024Article
- Article
- Coordinated alternation of DNA methylation and alternative splicing of PBRM1 affect bovine sperm structure and motility.Epigenetics · 2023Article
- Efficiently quantifying DNA methylation for bulk- and single-cell bisulfite data.Bioinformatics (Oxford, England) · 2023Article
- Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse Brain.bioRxiv : the preprint server for biology · 2023Article
- MARVEL: an integrated alternative splicing analysis platform for single-cell RNA sequencing data.Nucleic acids research · 2023Article
- Single-Cell RNA Sequencing Reveals New Basic and Translational Insights in the Cystic Fibrosis Lung.American journal of respiratory cell and molecular biology · 2023Review
- Position-dependent effects of RNA-binding proteins in the context of co-transcriptional splicing.NPJ systems biology and applications · 2023Article
- The emerging field of opportunities for single-cell DNA methylation studies in hematology and beyond.Frontiers in molecular biosciences · 2023Article
- Diverse cell-specific patterns of alternative polyadenylation in Drosophila.Nature communications · 2022Article
- SCAPE: a mixture model revealing single-cell polyadenylation diversity and cellular dynamics during cell differentiation and reprogramming.Nucleic acids research · 2022Article
- Heterogeneous Skeletal Muscle Cell and Nucleus Populations Identified by Single-Cell and Single-Nucleus Resolution Transcriptome Assays.Frontiers in genetics · 2022Review
- Plant Gravitropism: From Mechanistic Insights into Plant Function on Earth to Plants Colonizing Other Worlds.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Spatial Multiomics Analysis Reveals Only Minor Genetic and Epigenetic Changes in Human Liver Cancer Stem-Like Cells Compared With Other Tumor Parenchymal Cells.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAlternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic features, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remains poorly understood.
resultsWe applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results show that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on genomic features as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons. These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.
conclusionsOur study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.
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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.