The protracted timeline of maturation is a major bottleneck in generating adult-like neurons from human pluripotent stem cells. We identify a combination of four chemicals that promotes neuronal maturation by repressing epigenetic factors that inhibit it and stimulating activity-dependent factors that promote it.
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Fig. 1: Chemical screen for drivers of neuronal maturation.
References
Espuny-Camacho, I. et al. Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo. Neuron77, 440–456 (2013). This paper demonstrates that protracted human neuron maturation is maintained when hPSCs are transplanted into the mouse brain.
Article
CAS
PubMed
Google Scholar
Alvarez-Dominguez, J. R. & Melton, D. A. Cell maturation: hallmarks, triggers, and manipulation. Cell185, 235–249 (2022). A review article discussing the challenges of cell maturation across cell types.
Article
CAS
PubMed
PubMed Central
Google Scholar
Iwata, R. et al. Mitochondria metabolism sets the species-specific tempo of neuronal development. Science379, eabn4705 (2023). A paper showing that mitochondrial metabolism regulates neuronal maturation.
Article
CAS
PubMed
Google Scholar
Ciceri, G. et al. An epigenetic barrier sets the timing of human neuronal maturation. Preprint at bioRxiv https://doi.org/10.1101/2022.06.02.490114 (2022). This preprint describes detailed molecular signatures of human neuron maturation and identifies an epigenetic barrier in neural precursors that sets the pace of neuronal maturation.
Studer, L., Vera, E. & Cornacchia, D. Programming and reprogramming cellular age in the era of induced pluripotency. Cell Stem Cell16, 591–600 (2015). A short review that lays out the broader timing challenges in human stem cell models, from fate specification to maturation and aging.
Article
CAS
PubMed
PubMed Central
Google Scholar
Download references
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This is a summary of: Hergenreder, E. et al. Combined small-molecule treatment accelerates maturation of human pluripotent stem cell-derived neurons. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-02031-z (2024).
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Identification of a chemical cocktail that drives the maturation of human neurons.
Nat Biotechnol (2024). https://doi.org/10.1038/s41587-023-02044-8
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Published: 02 January 2024
DOI: https://doi.org/10.1038/s41587-023-02044-8
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