2026/05/13 by Anthony T. Bejjani, Alec Pankow, Ava R. Lamberty +26 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Single-cell and spatial transcriptomics #interferon and immune responses #Genomics and Chromatin Dynamics
paper · doi:10.64898/2026.05.09.724010
openalex publication_date 2026/05/13 · openalex created_date 2026/05/14 · openalex updated_date 2026/07/27
The human airway epithelium (HAE) is composed of diverse cell types that coordinate essential functions and host defenses. Among these defenses, interferons (IFNs) are central to antiviral programs. However, the gene regulatory networks (GRNs) governing HAE cellular identities and their IFN responses are incompletely defined. At single-cell resolution, we characterized the transcriptomes and accessible chromatin landscapes of HAE cell types, at steady state and following IFNβ stimulation. The resulting scRNA-seq and snATAC-seq data informed genome-scale GRN construction and inference of transcriptional circuits underlying cell identities. In response to IFN, we identified a shared transcriptional program across HAE cell types, and an expanded set of interferon-responsive genes exhibiting cell type-associated expression patterns. Cell type-associated transcription factors and chromatin accessibility contribute to distinct IFN-responsive gene expression programs. Together, these data provide a blueprint for molecular regulation of complex HAE responses and a foundation for therapeutic strategies to enhance host antiviral defense.