Comparative Transcriptomic Profiling in Two Widely Used Human Cell Lines Delineates Their Shared and Distinct Patterns of Interferon Responses

Abstract

Simple Summary Interferons (IFNs) are critical for pathogen resistance and immune modulation. While IFN response occurs in many cell types, a high-resolution comparison across cell types is lacking. By using RNA sequencing, this study conducted a time-serial charting of the transcriptomic responses in two widely used immortalized human cell lines, HeLa and HEK293T, during IFN-γ stimulation. We uncover stronger IFN response in HeLa cells, regarding the global transcriptomic dynamics, the number of IFN-stimulated genes (ISGs), and the level of ISG expression. Both cell lines share a core set of ISGs associated with canonical JAK-STAT signaling, yet HeLa uniquely activates additional inflammatory and adaptive immunity-related pathways. Despite the much weaker IFN response in HEK293T cells, we still identified a few HEK293T-specific ISGs, including several crucial immune-related genes. Notably, transposable elements—including many adjacent to ISGs—are also highly up-regulated in HeLa cells, implying their potential links to ISG induction. Collectively, this study provides a temporal atlas of IFN-γ stimulated transcriptomic dynamics in HeLa and HEK293T cells, which reveals the shared core module and cell-specific patterns of their interferon responses.