CRISPR Maps T Cells Gene by Gene

Functional screening decodes the link between genetic sequence and cell state

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A genome-scale screen mapped gene regulation in primary human CD4-positive T cells using CRISPR interference and single-cell RNA sequencing.
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The study analyzed approximately 22 million cells from four healthy donors, linking gene activity to immune responses and autoimmune disease susceptibility.
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Researchers identified over 2 million gene-to-gene regulatory effects, with many dependent on cellular context and T cell activation state.
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The analysis revealed 1,556 gene disruptions affecting cytokine production, including established T cell receptor signaling components.
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Limitations included the use of cells from only four donors and the inability to capture tissue-specific environments or all T cell polarization states.

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