ArticleNature genetics2025
Dissecting the impact of transcription factor dose on cell reprogramming heterogeneity using scTF-seq.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- A transcription factor regulatory atlas for activity inference and perturbation prediction.Nucleic acids research · 2026Article
- Systematic comparison of estimates of transcription factor activity by ATAC-seq and multiplexed reporter assays.Molecular systems biology · 2026Article
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Protocol for identifying cellular reprogramming minimal networks using combinatorial transcription factor screening.STAR protocols · 2026Article
- Computational blueprints for cell fate programming.Stem cell reports · 2026Review
- Gene regulatory networks: from correlative models to causal explanations.Nature reviews. Genetics · 2026Review
- Isoform-specific single-cell perturb-seq reveals distinct functions of alternative promoters in drug response.Nucleic acids research · 2026Article
- Nonlinear transcriptional responses to gradual modulation of transcription factor dosage.eLife · 2026Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Induced pluripotent stem cell reprogramming: methodological evolution and challenges in clinical translation.Frontiers in cell and developmental biology · 2026Review
- Systematic characterization of existing and novel inducible transgenic systems in human pluripotent stem cells after prolonged differentiation.bioRxiv : the preprint server for biology · 2025Article
- Compact transcription factor cassettes generate functional, engraftable motor neurons by direct conversion.Cell systems · 2025Article
- Optimized reporters for multiplexed detection of transcription factor activity.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
Reprogramming often yields heterogeneous cell fates, yet the underlying mechanisms remain poorly understood. To address this, we developed single-cell transcription factor sequencing (scTF-seq), a single-cell technique that induces barcoded, doxycycline-inducible TF overexpression and quantifies TF dose-dependent transcriptomic changes. Applied to mouse embryonic multipotent stromal cells, scTF-seq generated a gain-of-function atlas for 384 mouse TFs, identifying key regulators of lineage specification, cell cycle control and their interplay. Leveraging single-cell resolution, we uncovered how TF dose shapes reprogramming heterogeneity, revealing both dose-dependent and stochastic cell state transitions. We classified TFs into low-capacity and high-capacity groups, with the latter further subdivided by dose sensitivity. Combinatorial scTF-seq demonstrated that TF interactions can shift from synergistic to antagonistic depending on the relative dose. Altogether, scTF-seq enables the dissection of TF function, dose and cell fate control, providing a high-resolution framework to understand and predict reprogramming outcomes, advancing gene regulation research and the design of cell engineering strategies.
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