ArticleNature genetics2022
Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 86 citations in OpenAlex.
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- Engineered dCas12f1-SAM enables robust transcriptional activation and gain-of-function screening in primary human cells.Nature communications · 2026Article
- Dissecting PGENature communications · 2026Article
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- CRISPR-Cas9 Screening and Simulated Infection Transcriptomic Identify Key Drivers of Innate Immunity in Bactrian Camels.Animals : an open access journal from MDPI · 2026Article
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- FOXP3 expression depends on cell-type-specific cis-regulatory elements and transcription factor circuitry.Immunity · 2026Article
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- A comparison of computational methods for expression forecasting.Genome biology · 2025Article
- Gene regulatory network structure informs the distribution of perturbation effects.PLoS computational biology · 2025Article
- Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025Review
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- Trans-eQTL hotspots shape complex traits by modulating cellular states.Cell genomics · 2025Article
- Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq.bioRxiv : the preprint server for biology · 2025Article
- Cis-Regulatory Element and Transcription Factor Circuitry Required for Cell-Type Specific Expression of FOXP3.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Gene regulatory networks ensure that important genes are expressed at precise levels. When gene expression is sufficiently perturbed, it can lead to disease. To understand how gene expression disruptions percolate through a network, we must first map connections between regulatory genes and their downstream targets. However, we lack comprehensive knowledge of the upstream regulators of most genes. Here, we developed an approach for systematic discovery of upstream regulators of critical immune factors-IL2RA, IL-2 and CTLA4-in primary human T cells. Then, we mapped the network of the target genes of these regulators and putative cis-regulatory elements using CRISPR perturbations, RNA-seq and ATAC-seq. These regulators form densely interconnected networks with extensive feedback loops. Furthermore, this network is enriched for immune-associated disease variants and genes. These results provide insight into how immune-associated disease genes are regulated in T cells and broader principles about the structure of human gene regulatory networks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.