Radiofrequency regulates the BET-mediated pathways in radial glia differentiation in human cortical development
The human brain represents one of the most complex organs in our body, with development regulated by an intricate genetic program. Recently, non-genetic factors, such as prenatal stress, infection, and diet, have been shown to influence brain development. Radiofrequency radiation (RF; 800-2,400 MHz), emitted by natural and artificial sources such as microwaves and cell phones, represents a non-invasive environmental factor. Using human cortical organoids (hCOs) derived from human embryonic stem cells (hESCs), we investigate RF's effects on corticogenesis. We find that RF exposure regulates the differentiation of human and non-human primate radial glia progenitors, maintaining stem cell identity and delaying differentiation. Neurons differentiated under RF treatment show induction of expression of human endogenous retroviruses. Importantly, inhibitors for the BET (bromodomain and extraterminal) protein rescue RF-induced developmental defects in hCOs. Our findings reveal a mechanism by which RF modulates early brain development, offering a non-biological approach to regulate neural stem cell self-renewal.
Authors
- Mu Seog Choe
- Young‐Jin Kang
- Bhushan Dharmadhikari (ORCID: https://orcid.org/0000-0003-1626-5639)
- Nicola Micali (ORCID: https://orcid.org/0009-0002-2936-4708)
- Yoshiaki Tanaka (ORCID: https://orcid.org/0000-0002-2078-9374)
- Yangfei Xiang (ORCID: https://orcid.org/0000-0002-6256-6312)
- Pasko Rakić (ORCID: https://orcid.org/0000-0002-6963-0508)
- Prabir Patra (ORCID: https://orcid.org/0000-0002-2917-793X)
- Benjamin Patterson (ORCID: https://orcid.org/0009-0008-4132-9407)
- Y.C. Cho (ORCID: https://orcid.org/0000-0002-3100-240X)
- Woo Sub Yang (ORCID: https://orcid.org/0000-0002-2358-8287)
- Jonghun Kim (ORCID: https://orcid.org/0000-0002-9154-5529)
- Ferdi Rıdvan Kiral (ORCID: https://orcid.org/0000-0002-7006-9332)
- Sang-Hun Lee (ORCID: https://orcid.org/0000-0001-8880-2785)
- Mei Zhong (ORCID: https://orcid.org/0000-0003-2149-2772)
- Bilal Çakir (ORCID: https://orcid.org/0000-0003-4610-0317)
- In-Hyun Park
Institutions
- Minnesota State University, Mankato (US)
- University of Bridgeport (US)
- Yale Cancer Center (US)
- Yale University (US)
- Colorado State University (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1016/j.celrep.2025.116238
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Yale University
- NOMIS Stiftung
- National Institutes of Health
- National Institute on Drug Abuse