ArticleCell systems2025
Proliferation history and transcription factor levels drive direct conversion to motor neurons.
Article in Cell systems, 2025. 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.
- Luck favors the prepared in hepatic conversion.Stem cell reports · 2026Article
- Hepatic reprogramming occurs in a time-independent manner via an initial asymmetric division and continued mitotic activity.Stem cell reports · 2026Article
- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- Promoter editing generates stable setpoints of gene expression.Nature biotechnology · 2026Article
- Distinct media requirements for dopaminergic neuron reprogramming from human glia and fibroblasts.Scientific reports · 2026Article
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- Post-replicative chromatin accessibility predicts cell fate change.Stem cell reports · 2026Article
- Redefining cellular reprogramming with advanced genomic technologies.Nature reviews. Genetics · 2026Review
- Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026Article
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- MicroRNA-mediated neuronal detargeting alters astrocyte cell fate conversion trajectories in vivo.Communications biology · 2025Article
- Article
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.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
- Programmable promoter editing for precise control of transgene expression.bioRxiv : the preprint server for biology · 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
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7 authors.
Funding
Abstract
The sparse and stochastic nature of conversion has obscured our understanding of how transcription factors (TFs) drive cells to new identities. To overcome this limit, we develop a tailored, high-efficiency conversion system that increases the direct conversion of fibroblasts to motor neurons 100-fold. By tailoring the cocktail to a minimal set of transcripts, we reduce extrinsic variation, allowing us to examine how proliferation and TFs synergistically drive conversion. We show that cell state-as set by proliferation history-defines how cells interpret the levels of TFs. Controlling for proliferation history and titrating each TF, we find that conversion correlates with levels of the pioneer TF Ngn2. By isolating cells by both their proliferation history and Ngn2 levels, we demonstrate that levels of Ngn2 expression alone are insufficient to predict conversion rates. Rather, proliferation history and TF levels combine to drive direct conversion. Finally, increasing the proliferation rate of adult human fibroblasts generates morphologically mature induced human motor neurons at high rates.
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