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

Aug 2026 · Biology · Vol 15, pp. 1418 · 0 citations · 68 references
Medicine

TL;DR

A temporal atlas of IFN-γ stimulated transcriptomic dynamics in HeLa and HEK293T cells is provided, which reveals the shared core module and cell-specific patterns of their 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.

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