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Genome-scale perturb-seq in primary human CD4+ T cells reveals genes regulating T cell programs and human immune traits.

GSE314342 Homo sapiens Expression profiling by high throughput sequencing 577 samples Submitted 2026/02/06 Platform GPL34762Platform GPL34284
Summary
CD4+ T cells orchestrate immune responses against infection and cancer, yet a comprehensive map of their gene regulatory networks has been lacking. Perturb-seq enables systematic mapping of such networks, but large-scale application in primary human T cells has been challenging. Here, we developed a scalable, probe-based Perturb-seq platform and performed genome-scale perturbations of all expressed genes across 22 million primary CD4+ T cells from four donors under three stimulation conditions. We demonstrate the utility of this dataset in three ways. First, we identify previously unrecognized regulators of the two important immune cytokines, IL-10 and IL-21. Second, we show that ex vivo perturbation signatures can model T cell states observed in population-scale atlases, revealing regulators of helper T cell polarization and T cell aging. Third, we leverage regulatory relationships to mechanistically explain gene–trait associations in immune-related diseases, nominating genes for uncharacterized immune functions. Thus genome-scale perturb-seq in primary human T cells provides a foundational resource for decoding immune variation in humans and reprogramming T cell states for next-generation precision therapies.
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Direct links to NCBI, no account and no request form: the whole study as GSE314342_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 577 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1359008 and SRA study SRP643211. Searching any of these in the dataset finder brings you back here.

Study design
40 × scRNA-seq CRISPR interference screen of CD4+, ⍺β T cells, 2 pooled donors, resting and 8 hr stim

Supports a between-group comparison across 40 samples.

1 replicated groups read from the first 40 of 577 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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