ArticleDevelopment (Cambridge, England)2014
The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 102 citations in OpenAlex.
- Phosphorylation-dependent control of transcription factor activity regulates temporal patterning of cortical cell fate specification.Nature communications · 2026Article
- Comparative ASCL1 Interactome Analysis Reveals CDK2-Cyclin A2 as Suppressors of Differentiation in MYCN-Amplified Neuroblastoma.Molecular cancer research : MCR · 2026Article
- Ascl1 promotes OPC specification across species and central nervous system regions and its gliogenic function is regulated by phosphorylation.Developmental biology · 2026Article
- Phosphorylation and DNA damage resolution coordinate SOX2-mediated reprogramming in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A low-level Cdkn1c/p57EMBO reports · 2026Article
- A conserved differentiation programme facilitates inhibitory neuron production in the developing mouse and human cerebellum.Development (Cambridge, England) · 2025Article
- Coupling and decoupling of the cell cycle from cell differentiation in development.Development (Cambridge, England) · 2025Review
- Article
- Distinct proliferative and neuronal programmes of chromatin binding and gene activation by ASCL1 are cell cycle stage-specific.Development (Cambridge, England) · 2025Article
- Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.Open biology · 2025Review
- Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming.Development (Cambridge, England) · 2024Article
- ASCL1 regulates and cooperates with FOXA2 to drive terminal neuroendocrine phenotype in prostate cancer.JCI insight · 2024Article
- Transcription factors ASCL1 and OLIG2 drive glioblastoma initiation and co-regulate tumor cell types and migration.Nature communications · 2024Article
- Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site-deficient Ascl1.Science advances · 2024Article
- Distinct Regulation of ASCL1 by the Cell Cycle and Chemotherapy in Small Cell Lung Cancer.Molecular cancer research : MCR · 2024Article
- Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1.Nature neuroscience · 2024Article
- Inhibition of Microglial Activation Ameliorates Inflammation, Reduced Neurogenesis in the hippocampus, and Impaired Brain Function in a Rat Model of Bilirubin Encephalopathy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Article
- Insights and applications of direct neuronal reprogramming.Current opinion in genetics & development · 2023Review
- Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Generation of neurons from patient fibroblasts using a combination of developmentally defined transcription factors has great potential in disease modelling, as well as ultimately for use in regeneration and repair. However, generation of physiologically mature neurons in vitro remains problematic. Here we demonstrate the cell-cycle-dependent phosphorylation of a key reprogramming transcription factor, Ascl1, on multiple serine-proline sites. This multisite phosphorylation is a crucial regulator of the ability of Ascl1 to drive neuronal differentiation and maturation in vivo in the developing embryo; a phosphomutant form of Ascl1 shows substantially enhanced neuronal induction activity in Xenopus embryos. Mechanistically, we see that this un(der)phosphorylated Ascl1 is resistant to inhibition by both cyclin-dependent kinase activity and Notch signalling, both of which normally limit its neurogenic potential. Ascl1 is a central component of reprogramming transcription factor cocktails to generate neurons from human fibroblasts; the use of phosphomutant Ascl1 in place of the wild-type protein significantly promotes neuronal maturity after human fibroblast reprogramming in vitro. These results demonstrate that cell-cycle-dependent post-translational modification of proneural proteins directly regulates neuronal differentiation in vivo during development, and that this regulatory mechanism can be harnessed to promote maturation of neurons obtained by transdifferentiation of human cells in vitro.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.