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Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171737 | GEO | 2021/04/26

REPOSITORIES: GEO

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Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks.

Project description: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.

| S-EPMC10035359 | biostudies-literature

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [Amplicon]

Project description:Complex gene regulatory networks ensure that important genes are expressed at precise levels. When gene expression within these networks is sufficiently perturbed it can lead to disease. To understand how gene expression disruptions percolate through a network, we must first map the connections between regulatory genes and their downstream targets. However, it has been challenging to identify the upstream regulators for genes of interest. Here we develop a system for systematic discovery of upstream regulators of critical immune factors – IL2RA, IL-2, and CTLA4 – in primary human T cells. Then, CRISPR perturbations coupled with RNA-Seq, and ATAC-Seq, allowed us to map the full network of these regulators’ target genes and enhancers. These regulators form highly interconnected networks with extensive feedback loops. Furthermore, this network is highly enriched for autoimmune-associated disease variants and genes. These results provide insight into how autoimmune associated disease genes are regulated in T cells as well as broader principles about the structure of human gene regulatory networks.

2021-04-26 | GSE171678 | GEO

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [CRISPR]

2021-04-26 | GSE171674 | GEO

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [ATAC-Seq]

2021-04-26 | GSE171736 | GEO

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [RNA-Seq]

2021-04-26 | GSE171677 | GEO

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [Amplicon III]

2021-11-25 | GSE189523 | GEO

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [Amplicon II]

2021-11-25 | GSE189522 | GEO

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks

Project description:Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks

| PRJNA720685 | ENA

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [CRISPR]

Project description:Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [CRISPR]

| PRJNA720549 | ENA

Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [Amplicon]

Project description:Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks [Amplicon]

| PRJNA720559 | ENA

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