R-loop landscapes in the developing human brain are linked to neural differentiation and cell type-specific transcription.
Publication/Presentation Date
4-13-2026
Abstract
Here, we construct genome-scale maps of R-loops, three-stranded nucleic acid structures comprised of a DNA/RNA hybrid and a displaced single strand of DNA, in both proliferative and differentiated zones of the human prenatal brain. We show that R-loops are abundant in the progenitor-rich germinal matrix and preferentially form at gene promoters slated for upregulated expression at later stages of differentiation, including numerous neurodevelopmental risk genes. RNase H1-mediated contraction of the genomic R-loop space in neural progenitors shifted differentiation toward the neuronal lineage and was associated with transcriptomic alterations, along with defective functional and structural neuronal connectivity in vivo and in vitro. Therefore, we conclude that R-loops are important for fine-tuning differentiation-sensitive gene expression programs of neural progenitor cells.
Volume
16
Issue
1
ISSN
2158-3188
Published In/Presented At
LaMarca, E. A., Saito, A., Plaza-Jennings, A., Espeso-Gil, S., Hellmich, A., Fernando, M. B., Javidfar, B., Liao, W., Estill, M., Townsley, K., Florio, A., Ethridge, J. E., Do, C., Tycko, B., Shen, L., Kamiya, A., Tsankova, N. M., Brennand, K. J., & Akbarian, S. (2026). R-loop landscapes in the developing human brain are linked to neural differentiation and cell type-specific transcription. Translational psychiatry, 16(1), 250. https://doi.org/10.1038/s41398-026-04009-2
Disciplines
Medicine and Health Sciences
PubMedID
41974678
Department(s)
Medical Education
Document Type
Article