FGF8-mediated gene regulation affects regional identity in human cerebral organoids
- University Côte d'Azur, France
- Université Cote d'Azur, France
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
Abstract
The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic domains, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.
Data availability
The raw data from the single-cell RNA sequencing (scRNA-seq) experiments have been deposited in the NCBI Gene Expression Omnibus (GEO) and are publicly available under the accession number GSE276558. Further details can be accessed at the linked repository. Additional data for the graphs of immunostaining pixel intensity, cell counting, or real-time RT-PCR are provided as Source data linked to the images.
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FGF8-mediated gene regulation affects regional identity in human cerebral organoidsNCBI Gene Expression Omnibus, GSE276558.
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Funding
Agence Nationale de la Recherche (IDEX UCAJedi ANR-15-IDEX-01)
- Michèle Studer
Fondation pour la Recherche Médicale (EQU202003010222)
- Michèle Studer
Fondation de France (00123416)
- Michèle Studer
Agence Nationale de la Recherche (ANR-21-NEU2-0003-03)
- Michèle Studer
Agence Nationale de la Recherche (ANR-10-INBS-0009)
- Matthieu Jung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2024, Bertacchi et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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FGF8-mediated gene regulation affects regional identity in human cerebral organoids
eLife 13:e98096.
https://doi.org/10.7554/eLife.98096
