ArticleNature communications2023
Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Potentiated Maturation of hPSC-Derived Dopaminergic Neurons via Convergent Genetic and Small Molecule Modulation.Tissue engineering and regenerative medicine · 2026Article
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Aberrant neuronal differentiation and splicing defects in Congenital Myotonic Dystrophy (DM1) iPSC models.bioRxiv : the preprint server for biology · 2026Article
- Neurogenin-2 Reprograms Human Microglial Lineage Cells into Neurons In Vitro and in Chimeric Brains.bioRxiv : the preprint server for biology · 2026Article
- Nrf2 overexpression reprograms neural stem cell fate: promoting neuronal differentiation and functional recovery post-ischemic stroke via suppression of the ROS/NF-κB axis.Journal of translational medicine · 2026Article
- Temporal Transcriptional Regulation of Human Neuronal Differentiation via Forward Programming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatiotemporal-controlled ultrasound-driven Li-PDA@ZnO nanoparticles promote neural stem cell differentiation synergy with biohydrogel repair spinal cord injury.Bioactive materials · 2026Article
- Identifying key regulators in neuronal transdifferentiation by gene regulatory network analysis.PNAS nexus · 2025Article
- Rapid generation of ventral A9-like dopaminergic neurons from patterned iPSCs.bioRxiv : the preprint server for biology · 2025Article
- Neocortical neurogenesis: a proneural gene perspective.The FEBS journal · 2025Review
- Neuronal Differentiation and Exosome Profiling of Dental Pulp Stem Cells: Unveiling Their Potential for Nerve Repair.International journal of molecular sciences · 2025Article
- CETN3 deficiency induces microcephaly by disrupting neural stem/progenitor cell fate through impaired centrosome assembly and RNA splicing.EMBO molecular medicine · 2025Article
- 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
- Proliferation history and transcription factor levels drive direct conversion to motor neurons.Cell systems · 2025Article
- Article
- The chemotherapy agent doxorubicin induces CNS expression of Ascl1, a regulator of adult neurogenesis and differentiation.Scientific reports · 2025Article
- Article
- Transcriptomic profiling of neural cultures from the KYOU iPSC line via alternative differentiation protocols.Frontiers in molecular neuroscience · 2025Article
- Schizophrenia risk gene ZNF536 modulates retinoic acid response and neuronal gene networks in SH-SY5Y cells.Frontiers in molecular neuroscience · 2025Article
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Authors and funding
9 authors.
Funding
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Abstract
Ascl1 and Ngn2, closely related proneural transcription factors, are able to convert mouse embryonic stem cells into induced neurons. Despite their similarities, these factors elicit only partially overlapping transcriptional programs, and it remains unknown whether cells are converted via distinct mechanisms. Here we show that Ascl1 and Ngn2 induce mutually exclusive side populations by binding and activating distinct lineage drivers. Furthermore, Ascl1 rapidly dismantles the pluripotency network and installs neuronal and trophoblast cell fates, while Ngn2 generates a neural stem cell-like intermediate supported by incomplete shutdown of the pluripotency network. Using CRISPR-Cas9 knockout screening, we find that Ascl1 relies more on factors regulating pluripotency and the cell cycle, such as Tcf7l1. In the absence of Tcf7l1, Ascl1 still represses core pluripotency genes but fails to exit the cell cycle. However, overexpression of Cdkn1c induces cell cycle exit and restores the generation of neurons. These findings highlight that cell type conversion can occur through two distinct mechanistic paths, even when induced by closely related transcription factors.
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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 Socratic graph.