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GSDMD-mediated metabolic crosstalk licenses a pro-regenerative niche for tissue repair

ABSTRACT: GSDMD-mediated metabolic crosstalk licenses a pro-regenerative niche for tissue repair

PROVIDER: PRJNA1051656 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27193478_1.fastq.gz	Fastqsanger.gz
	SRR27193478_2.fastq.gz	Fastqsanger.gz
	SRR27193479_1.fastq.gz	Fastqsanger.gz
	SRR27193479_2.fastq.gz	Fastqsanger.gz
	SRR27193480_1.fastq.gz	Fastqsanger.gz

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GSDMD-mediated metabolic crosstalk licenses a pro-regenerative niche for tissue repair

Project description:The establishment of an early pro-regenerative niche is crucial for tissue regeneration. Gasdermin D (GSDMD)-dependent pyroptosis accounts for the release of inflammatory cytokines upon various insults. However, little is known about its role in tissue regeneration followed by homeostatic maintenance. Here, we show that macrophage GSDMD deficiency delayed tissue recovery, with little impact on the local inflammatory milieu or the lytic pyroptosis process. Metabolite secretome profiling of hyperactivated macrophages unveiled the non-canonical metabolite-secreting function of GSDMD. And we further identified 11,12-epoxyeicosatrienoic acid (11,12-EET) as a bioactive pro-healing oxylipin, secreted from hyperactive macrophages in a GSDMD-dependent manner. Indeed, accumulation of 11,12-EET by direct supplementation or deletion of its hydrolytic enzyme Ephx2 accelerated muscle regeneration. We further demonstrated that the Ephx2 level accumulated within aged muscle, which led to a decreased intramuscular 11,12-EET level. And consecutive 11,12-EET treatment rejuvenated aged muscle. Mechanistically, 11,12-EET amplifies fibroblast growth factor/FGF receptor (FGF-FGFR) signaling by modulating FGF liquid-liquid phase separation, hence boosting the activation and proliferation of muscle stem cells (MuSCs). These data depict a GSDMD-guided metabolite crosstalk between macrophages and MuSCs that governs the repair process, which offers new therapeutic insights for the regeneration of injured or aged tissues.

2024-07-29 | GSE250049 | GEO

Transcriptional Activation of Regenerative Haematopoiesis via Niche Sensing

Project description:Transcriptional Activation of Regenerative Haematopoiesis via Niche Sensing

| PRJNA716599 | ENA

Netrin-1 engineered endothelial cell exosomes induce the formation of pre-regenerative niche to accelerate peripheral nerve repair

Project description:The formation of vascular niche is pivotal during the early stage of peripheral nerve regeneration. This antecedent angiogenesis meets the nutrient requirements for subsequent rapid axon regeneration and remyelination. Nevertheless, the mechanisms of vascular niche in the regulation of peripheral nerve remain unclear. The axon guidance molecule Netrin-1 (NTN1) is widely expressed in peripheral nerves and particularly was found up-regulated in sciatic nerve stump after peripheral nerve injury (PNI). Herein, we demonstrated that NTN1-high endothelial cells (NTN1+ECs) were the critical component of vascular niche, fostering angiogenesis, axon regeneration and repair-related phenotypes. And we also found that NTN1+ECs derived exosomes (NTN1 EC-EXO) were involved in the formation of vascular niche as a critical role. Multi-omics analysis further verified that NTN1 EC-EXO carried a low-level expression of let7a-5p and activated key pathways associated with niche formation including focal adhesion, axon guidance, PI3K-AKT signaling pathway and mTOR signaling pathway. Taken together, our findings suggested the potential construction of a pre-regenerative niche induced by NTN1 EC-EXO, thereby establishing a conductive microenvironment for nerve repair and facilitating the functional recovery after PNI in the early injury phase.

2024-05-17 | PXD051130 | Pride

A palmitoylation-depalmitoylation relay spatiotemporally controls GSDMD activation in pyroptosis [II]

Project description:Gasdermin D (GSDMD) is the executioner of pyroptosis, which is important for host defense against pathogen infection. After activation, caspase-mediated cleavage of GSDMD liberates an N-terminal fragment (GSDMD-NT), which oligomerizes and forms pores in the plasma membrane, leading to cell death and subsequent release of proinflammatory cytokines. How this process is spatiotemporally controlled to promote pyroptosis in cells has been a fundamental, unaddressed question. Here, we identify GSDMD as a substrate for reversible S-palmitoylation on cysteine 192 (Cys192) in response to lipopolysaccharide (LPS) stimulation. We found that the palmitoyl acyltransferase DHHC7palmitoylates GSDMD to direct its cleavage by caspases in pyroptosis by promoting the interaction of GSDMD and caspases. We further show that after GSDMD cleavage, palmitoylation of GSDMD-NTpromotes its plasma membrane translocation and binding, and then acyl protein thioesterase 2 (APT2) depalmitoylates GSDMD-NT to unmask the Cys192 residue to promote oxidation-mediated oligomerization and pyroptosis. Perturbation of either palmitoylation or depalmitoylation suppresses pyroptosis, extends the survival of mice from LPS-induced lethal septic shock and sensitizes mice to bacterial infection. Thus. our findings reveal a model through which a palmitoylation-depalmitoylationrelay spatially and temporally controls GSDMD activation in pyroptosis.

2024-02-25 | GSE252911 | GEO

A palmitoylation-depalmitoylation relay spatiotemporally controls GSDMD activation in pyroptosis [I]

2024-02-25 | GSE252893 | GEO

RNA Sequencing Analysis of macrophages from Wild Type and Gsdmd-/- colitis mice

Project description:We identified that GSDMD protected against DDS-induced colitis, and GSDMD deficiency in macrophages promoted the development of DSS-induced colitis.The purpose of this experiment was to identify how GSDMD protected against DSS-induced colitis.

2020-07-06 | GSE137827 | GEO

Transcriptional Activation of Regenerative Haematopoiesis via Niche Sensing [Bulk H3K27ac ChIP]

Project description:Transcriptional Activation of Regenerative Haematopoiesis via Niche Sensing [Bulk H3K27ac ChIP]

| PRJNA716603 | ENA

Regulation of the alveolar regenerative niche by amphiregulin-producing Treg cells

Project description:Regulation of the alveolar regenerative niche by amphiregulin-producing Treg cells

| PRJNA715236 | ENA

Transcriptional Activation of Regenerative Haematopoiesis via Niche Sensing [Bulk ATAC-Seq]

Project description:Transcriptional Activation of Regenerative Haematopoiesis via Niche Sensing [Bulk ATAC-Seq]

| PRJNA716519 | ENA

RNA Sequencing Analysis of macrophage and CD4+T cells from Wild Type and Gsdmd-/- mice

Project description:We identified that GSDMD was required for the pathogenesis of EAE, and GSDMD deficiency in peripheral myeloid cells impaired the infiltration of immune cells into the CNS , leading to the suppression of neuroinflammation and demyelination.The purpose of this experiment was to identify how GSDMD induces EAE.

2019-08-22 | GSE126289 | GEO

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