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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
24,99 € / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
209,00 € per year
only 17,42 € per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Log in
Learn about institutional subscriptions
Read our FAQs
Contact customer support
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. Neuron 77, 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. Cell 185, 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. Science 379, 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 Cell 16, 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
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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).
About this article
Cite this article
Identification of a chemical cocktail that drives the maturation of human neurons.
Nat Biotechnol (2024). https://doi.org/10.1038/s41587-023-02044-8
Download citation
Published: 02 January 2024
DOI: https://doi.org/10.1038/s41587-023-02044-8
>>> Read full article>>>
Copyright for syndicated content belongs to the linked Source : Nature.com – https://www.nature.com/articles/s41587-023-02044-8
