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The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair [Alveolar macrophages]

ABSTRACT: We compare the transcriptional profile of Egr2-sufficient or Egr2-deficient airway macrophages obtained from Lyz2-Cre-Egr2-floxed mice

ORGANISM(S): Mus musculus

PROVIDER: GSE182043 | GEO | 2021/11/19

REPOSITORIES: GEO

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The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair.

Project description:Alveolar macrophages are the most abundant macrophages in the healthy lung where they play key roles in homeostasis and immune surveillance against airborne pathogens. Tissue-specific differentiation and survival of alveolar macrophages rely on niche-derived factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor–β (TGF-β). However, the nature of the downstream molecular pathways that regulate the identity and function of alveolar macrophages and their response to injury remain poorly understood. Here, we identify that the transcription factor EGR2 is an evolutionarily conserved feature of lung alveolar macrophages and show that cell-intrinsic EGR2 is indispensable for the tissue-specific identity of alveolar macrophages. Mechanistically, we show that EGR2 is driven by TGF-β and GM-CSF in a PPAR-γ–dependent manner to control alveolar macrophage differentiation. Functionally, EGR2 was dispensable for the regulation of lipids in the airways but crucial for the effective handling of the respiratory pathogen Streptococcus pneumoniae. Last, we show that EGR2 is required for repopulation of the alveolar niche after sterile, bleomycin-induced lung injury and demonstrate that EGR2-dependent, monocyte-derived alveolar macrophages are vital for effective tissue repair after injury. Collectively, we demonstrate that EGR2 is an indispensable component of the transcriptional network controlling the identity and function of alveolar macrophages in health and disease.

| S-EPMC7612216 | biostudies-literature

The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair

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

2021-11-19 | GSE182044 | GEO

The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair [Alveolar macrophages]

Project description:The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair [Alveolar macrophages]

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The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair [myeloid cells]

Project description:We profile the transcriptomes of over 3,000 mouse single myeloid cells from mouse lung to define the transcriptional profiles of monocytes and subsets of dendritic cells and macrophages. We perform differential gene expression analysis to determine the transcriptional regulators unique to each cluster.

2021-11-19 | GSE181894 | GEO

The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair

Project description:The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair

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The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair [myeloid cells]

Project description:The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair [myeloid cells]

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ATAC-seq in wild type and EGR2 knock-out mouse alveolar macrophages

Project description:The alveolar macrophages (AMs) as a component of the innate immunity of the lung play important role in the elimination of inhaled microbes and harmful agents. The transcription factor EGR2 is a known marker transcription factor of AMs but its exact epigenetic and transcriptomic effects have not been examined. In our study, we performed ATAC-seq and RNA-seq in WT and EGR2 deficient alveolar macrophages to describe the mechanism of action and to predict potential direct target genes of EGR2. Clec7a is one of the targets of this transcription factor which is essential in the zymosan-induced inflammatory response. We further analyzed this process by applying in vivo mouse model. Our findings demonstrate that EGR2 is a key transcriptional activator, responsible for the intact protective program against different pathogens, especially fungi in AMs.

2024-08-29 | GSE181085 | GEO

CUT&RUN in wild type and EGR2 knock-out mouse alveolar macrophages

Project description:The alveolar macrophages (AMs) as a component of the innate immunity of the lung play important role in the elimination of inhaled microbes and harmful agents. The transcription factor EGR2 is a known marker transcription factor of AMs but its exact epigenetic and transcriptomic effects have not been examined. In our study, we performed ATAC-seq, RNA-seq, and CUT&RUN in WT and EGR2 deficient alveolar macrophages to describe the mechanism of action and to predict potential direct target genes of EGR2. Clec7a is one of the targets of this transcription factor which is essential in the zymosan-induced inflammatory response. We further analyzed this process by applying in vivo mouse model. Our findings demonstrate that EGR2 is a key transcriptional activator, responsible for the intact protective program against different pathogens, especially fungi in AMs.

2024-08-29 | GSE202858 | GEO

RNA-seq in wild type and EGR2 knock-out mouse alveolar macrophages upon vehicle and zymosan treatment

2024-08-29 | GSE181086 | GEO

Wild type and EGR2 knock-out mouse alveolar macrophages

Project description:Wild type and EGR2 knock-out mouse alveolar macrophages

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