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CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [CRISPR screen]

ABSTRACT: CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [CRISPR screen]

PROVIDER: PRJNA1090067 | ENA |

REPOSITORIES: ENA

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CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [CRISPR screen]

Project description:Group 2 innate lymphoid cells (ILC2s) orchestrate tissue homeostasis, allergic disorders and anti-helminth protective immunity through their production of cytokines. However, their rarity has hampered high-throughput genetic screening approaches to uncover novel ILC2 regulators in an unbiased manner. We combined expansion of progenitors from multi-reporter mouse strains with optimised ILC differentiation cultures to perform CRISPR-Cas9 screens for regulators of ILC2 development and function. Mef2d emerged as a critical regulator of GATA3 and IL-13, and was essential for type-2 immunity as demonstrated by conditional Mef2d-deficient mice, including a Boolean-ILC2-Cre (BIC) mouse strain developed to enable ILC2-specific gene deletion. Mechanistically, Mef2d bound and transcriptionally repressed the Zc3h12a locus encoding the endonuclease Regnase-1, a negative regulator of IL-33 receptor (ST2) and GATA3 expression, thereby promoting IL-33-mediated ILC2 proliferation and cytokine production. Notably, in ILC2s Mef2d also acted downstream of leukotriene C4-induced calcium-mediated signalling to translocate NFAT1 to the nucleus to promote type-2 gene transcription. These Mef2d-mediated pathways converge and feedback to potentiate type-2 immunity.

2024-07-03 | GSE262028 | GEO

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ATAC-Seq]

2024-07-03 | GSE242146 | GEO

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ChIP-Seq]

2024-07-03 | GSE242030 | GEO

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity

Project description:CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity

| PRJNA1011854 | ENA

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ChIP-Seq]

Project description:CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ChIP-Seq]

| PRJNA1011237 | ENA

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ATAC-Seq]

Project description:CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [ATAC-Seq]

| PRJNA1011860 | ENA

CRISPR screens and ILC2-targeted Boolean circuitry reveal Mef2d-potentiation of type-2 immunity [RNA-Seq]

2024-06-28 | GSE242029 | GEO

CRISPR screen

Project description:CRISPR screen

| OEX00023089 | NODE

ILC2 development requires GATA3-related super-enhancers after lineage commitment

Project description:This SuperSeries is composed of the SubSeries listed below. Group 2 innate lymphoid cells (ILC2) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 being a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains elusive. Herein, we identified ILC2-specific tandem GATA3-related super-enhancers (G3SE) that induce high GATA3 in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 loss in the BM, lung, liver, and small intestine, a slight ILC1 increase, and no difference in ILC3, LTi, NK cells, nor Th2 cells. Single-cell RNA-sequencing revealed that GATA3 induction in late ILC2-committed precursors depends on G3SEs and is required for the transition to mature ILC2. Cnot6l, part of the CCR4-Not deadenylase complex, is a possible GATA3 target during ILC2 development. Our findings indicate a novel regulatory mechanism for GATA3 expression during ILC2 development.

2024-05-14 | GSE218155 | GEO

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-28 | GSE242147 | GEO