ArticleNature2016
Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 281 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
281 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022Pooled it
- Protracted Fate Acquisition and Epigenetic De-Aging During Induced Neural Stem Cell Conversion of Human Blood Cells.Aging cell · 2026Article
- Trajectory-informed gene feature selection in single-cell analysis with SEEK-VFI.Cell reports methods · 2026Article
- Modulating RNA condensates to control cell fate.Nature biotechnology · 2026Article
- Single cell analysis of developing Merkel cells reveals the emergence of non-coding RNA biotypes as a hallmark of terminal differentiation.Cell death and differentiation · 2026Article
- Inferring cell-specific gene regulatory networks based on causal graph embedding.Cell reports methods · 2026Article
- Harnessing Lessons from Gel-Based and Advanced Biomaterial Therapeutics to Enable Direct Cellular Reprogramming.Gels (Basel, Switzerland) · 2026Review
- Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons.Science advances · 2026Article
- Combinatorial transcription factor interactions drive modular gene regulatory networks.bioRxiv : the preprint server for biology · 2026Article
- From time-course expression to gene regulation: direct linear ODE inference without finite-difference approximation.bioRxiv : the preprint server for biology · 2026Article
- Simulation-guided chemical direct reprogramming informed by temporal cellular conversion processes at the single-cell level.Communications chemistry · 2026Article
- Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.Cell reports. Medicine · 2026Article
- ASCL1 promotes nuclear shrinkage in transdifferentiation by suppressing NUP37.Stem cell reports · 2026Article
- Redefining cellular reprogramming with advanced genomic technologies.Nature reviews. Genetics · 2026Review
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- scMix: learning temporal dynamics of gene expression under irregular time intervals.Bioinformatics (Oxford, England) · 2026Article
- Article
- Neural regulatory networks: challenges and opportunities in the treatment of psoriasis.Frontiers in immunology · 2026Review
- Direct neuronal reprogramming for neurological diseases: applications, translational Challenges, and future directions.Frontiers in neuroscience · 2026Review
- The Mechanisms and Application Prospects of Astrocyte Reprogramming into Neurons in Central Nervous System Diseases.Current neuropharmacology · 2026Review
221 more citing papers are in PubMed but not listed here.
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11 authors.
Funding
Abstract
Direct lineage reprogramming represents a remarkable conversion of cellular and transcriptome states. However, the intermediate stages through which individual cells progress during reprogramming are largely undefined. Here we use single-cell RNA sequencing at multiple time points to dissect direct reprogramming from mouse embryonic fibroblasts to induced neuronal cells. By deconstructing heterogeneity at each time point and ordering cells by transcriptome similarity, we find that the molecular reprogramming path is remarkably continuous. Overexpression of the proneural pioneer factor Ascl1 results in a well-defined initialization, causing cells to exit the cell cycle and re-focus gene expression through distinct neural transcription factors. The initial transcriptional response is relatively homogeneous among fibroblasts, suggesting that the early steps are not limiting for productive reprogramming. Instead, the later emergence of a competing myogenic program and variable transgene dynamics over time appear to be the major efficiency limits of direct reprogramming. Moreover, a transcriptional state, distinct from donor and target cell programs, is transiently induced in cells undergoing productive reprogramming. Our data provide a high-resolution approach for understanding transcriptome states during lineage differentiation.
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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.