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0Researchers developed a massive genome-scale perturb-seq platform to map the regulatory networks of 22 million primary human CD4+ T cells. By systematically knocking down over 12,000 genes across different activation states, they created a dynamic atlas that identifies how specific regulators control immune programs and cytokine production. The study demonstrates that gene regulatory effects change significantly depending on whether a cell is at rest or stimulated. Furthermore, the authors successfully used this data to predict the regulators responsible for T cell polarization and age-related immune changes observed in human populations. Finally, the work establishes a foundational resource that links specific molecular pathways to autoimmune disease susceptibility and human immune traits.
References:
Zhu R, Dann E, Yan J, et al. Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits[J]. Cell, 2025.
