ArticleProceedings of the National Academy of Sciences of the United States of America2024
Generation of human excitatory forebrain neurons by cooperative binding of proneural NGN2 and homeobox factor EMX1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Advancements in differentiation of induced pluripotent stem cells into specialized neuronal subtypes.Neural regeneration research · 2026Article
- Neurogenin-2 Reprograms Human Microglial Lineage Cells into Neurons In Vitro and in Chimeric Brains.bioRxiv : the preprint server for biology · 2026Article
- Article
- Advances in chemogenetics: a review of DREADDs and its application in psychiatric disorders.Molecular psychiatry · 2026Review
- Temporal Transcriptional Regulation of Human Neuronal Differentiation via Forward Programming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neocortical neurogenesis: a proneural gene perspective.The FEBS journal · 2025Review
- Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons.Neurobiology of disease · 2025Article
- Proteomics-based receptor-ligand matching enhances differentiation maturity of human-stem-cell-derived neurons.Stem cell reports · 2025Article
- Integrated multi-omic characterizations of the synapse reveal RNA processing factors and ubiquitin ligases associated with neurodevelopmental disorders.Cell systems · 2025Article
- Optimization of Transcription Factor-Driven Neuronal Differentiation from Human Induced Pluripotent Stem Cells for Disease Modelling and Drug Screening.Stem cell reviews and reports · 2025Article
- A Snapshot of Early Transcriptional Changes Accompanying the Pro-Neural Phenotype Switch by NGN2, ASCL1, SOX2, and MSI1 in Human Fibroblasts: An RNA-Seq Study.International journal of molecular sciences · 2024Article
- Fully defined NGN2 neuron protocol reveals diverse signatures of neuronal maturation.Cell reports methods · 2024Article
- Review
- Generation of human excitatory forebrain neurons by cooperative binding of proneural NGN2 and homeobox factor EMX1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Generation of defined neuronal subtypes from human pluripotent stem cells remains a challenge. The proneural factor NGN2 has been shown to overcome experimental variability observed by morphogen-guided differentiation and directly converts pluripotent stem cells into neurons, but their cellular heterogeneity has not been investigated yet. Here, we found that NGN2 reproducibly produces three different kinds of excitatory neurons characterized by partial coactivation of other neurotransmitter programs. We explored two principle approaches to achieve more precise specification: prepatterning the chromatin landscape that NGN2 is exposed to and combining NGN2 with region-specific transcription factors. Unexpectedly, the chromatin context of regionalized neural progenitors only mildly altered genomic NGN2 binding and its transcriptional response and did not affect neurotransmitter specification. In contrast, coexpression of region-specific homeobox factors such as EMX1 resulted in drastic redistribution of NGN2 including recruitment to homeobox targets and resulted in glutamatergic neurons with silenced nonglutamatergic programs. These results provide the molecular basis for a blueprint for improved strategies for generating a plethora of defined neuronal subpopulations from pluripotent stem cells for therapeutic or disease-modeling purposes.
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