ArticleGenome biology2021
Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 76 citations in OpenAlex.
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- STEER: decoupling kinetics with Spatial-Temporal Explainable Expert model for RNA velocity inference.National science review · 2026Article
- Interpretable learning of temporal cellular dynamics from single-cell data.Cell reports methods · 2026Article
- Neural network-assisted RNA velocity imputation for empowering transcript dynamics-based analyses.iScience · 2026Article
- Bayesian inference of RNA velocity incorporating timepoints, lineage bifurcations, and count data.PLoS computational biology · 2026Article
- Pseudotimecascade Visualizes Gene Expression Cascade in Pseudotime Analysis.Computational and structural biotechnology journal · 2026Article
- Multi-omic relay velocity modeling uncovers dynamic chromatin-transcription regulation across cell states.Nature communications · 2025Article
- A novel paradigm for single-cell annotation in stem cell research.Stem cell reports · 2025Review
- Inferring differential dynamics from multi-lineage, multi-omic, and multi-sample single-cell data with MultiVeloVAE.Nature communications · 2025Article
- Eomes directs the formation of spatially and functionally diverse extraembryonic hematovascular tissues.Developmental cell · 2025Article
- GraphVelo allows for accurate inference of multimodal velocities and molecular mechanisms for single cells.Nature communications · 2025Article
- spVelo: RNA velocity inference for multi-batch spatial transcriptomics data.Genome biology · 2025Article
- TIVelo: RNA velocity estimation leveraging cluster-level trajectory inference.Nature communications · 2025Article
- Paradigms, innovations, and biological applications of RNA velocity: a comprehensive review.Briefings in bioinformatics · 2025Review
- diffGEK: differential gene expression kinetics.Bioinformatics (Oxford, England) · 2025Article
- Cell2fate infers RNA velocity modules to improve cell fate prediction.Nature methods · 2025Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSingle-cell technologies are transforming biomedical research, including the recent demonstration that unspliced pre-mRNA present in single-cell RNA-Seq permits prediction of future expression states. Here we apply this RNA velocity concept to an extended timecourse dataset covering mouse gastrulation and early organogenesis.
resultsIntriguingly, RNA velocity correctly identifies epiblast cells as the starting point, but several trajectory predictions at later stages are inconsistent with both real-time ordering and existing knowledge. The most striking discrepancy concerns red blood cell maturation, with velocity-inferred trajectories opposing the true differentiation path. Investigating the underlying causes reveals a group of genes with a coordinated step-change in transcription, thus violating the assumptions behind current velocity analysis suites, which do not accommodate time-dependent changes in expression dynamics. Using scRNA-Seq analysis of chimeric mouse embryos lacking the major erythroid regulator Gata1, we show that genes with the step-changes in expression dynamics during erythroid differentiation fail to be upregulated in the mutant cells, thus underscoring the coordination of modulating transcription rate along a differentiation trajectory. In addition to the expected block in erythroid maturation, the Gata1-chimera dataset reveals induction of PU.1 and expansion of megakaryocyte progenitors. Finally, we show that erythropoiesis in human fetal liver is similarly characterized by a coordinated step-change in gene expression.
conclusionsBy identifying a limitation of the current velocity framework coupled with in vivo analysis of mutant cells, we reveal a coordinated step-change in gene expression kinetics during erythropoiesis, with likely implications for many other differentiation processes.
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