ArticleScience advances2023
Synthetic genetic circuits to uncover the OCT4 trajectories of successful reprogramming of human fibroblasts.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Long-Term Labeling and Differentiation Monitoring of Mouse Spermatogonial Stem Cells Using CellREADR.Biotech (Basel (Switzerland)) · 2026Article
- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- Synthetic tunable promoters for flexible control of multi-gene expression in mammalian cells.Journal of advanced research · 2025Article
- Engineering Cell Fate with Adaptive Feedback Control.ACS synthetic biology · 2025Article
- In silico modeling of directed differentiation of induced pluripotent stem cells to definitive endoderm.PLoS computational biology · 2025Article
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.Cell systems · 2025Article
- Proliferation history and transcription factor levels drive direct conversion to motor neurons.Cell systems · 2025Article
- Compact transcription factor cassettes generate functional, engraftable motor neurons by direct conversion.Cell systems · 2025Article
- Rewinding the Tape to Identify Intrinsic Determinants of Reprogramming Potential.Cellular reprogramming · 2024Article
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.bioRxiv : the preprint server for biology · 2024Article
- Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024Review
- Oct4 redox sensitivity potentiates reprogramming and differentiation.Genes & development · 2024Article
- Proliferation history and transcription factor levels drive direct conversion.bioRxiv : the preprint server for biology · 2023Article
- Transcription factor stoichiometry, motif affinity and syntax regulate single-cell chromatin dynamics during fibroblast reprogramming to pluripotency.bioRxiv : the preprint server for biology · 2023Article
- Deep Neural Networks for Predicting Single-Cell Responses and Probability Landscapes.ACS synthetic biology · 2023Article
- OCT4's role and mechanism underlying oral squamous cell carcinoma.Journal of Zhejiang University. Science. BArticle
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs) is inefficient, with heterogeneity among transcription factor (TF) trajectories driving divergent cell states. Nevertheless, the impact of TF dynamics on reprogramming efficiency remains uncharted. We develop a system that accurately reports OCT4 protein levels in live cells and use it to reveal the trajectories of OCT4 in successful reprogramming. Our system comprises a synthetic genetic circuit that leverages noise to generate a wide range of OCT4 trajectories and a microRNA targeting endogenous OCT4 to set total cellular OCT4 protein levels. By fusing OCT4 to a fluorescent protein, we are able to track OCT4 trajectories with clonal resolution via live-cell imaging. We discover that a supraphysiological, stable OCT4 level is required, but not sufficient, for efficient iPSC colony formation. Our synthetic genetic circuit design and high-throughput live-imaging pipeline are generalizable for investigating TF dynamics for other cell fate programming applications.
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