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Transcriptome of lung tissue from C57BL/6 mice with or without neutrophil depletion at ZT04 and ZT16

ABSTRACT: Transcriptome of lung tissue from C57BL/6 mice with or without neutrophil depletion at ZT04 and ZT16

PROVIDER: PRJNA416366 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6236020.fastq.gz	Fastqsanger.gz
	SRR6236030.fastq.gz	Fastqsanger.gz
	SRR6236040.fastq.gz	Fastqsanger.gz
	SRR6236021.fastq.gz	Fastqsanger.gz
	SRR6236031.fastq.gz	Fastqsanger.gz

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Transcriptome of lung tissue from C57BL/6 mice with or without neutrophil depletion at ZT04 and ZT16

Project description:Our study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)).

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Circadian transcriptional profile of tissues with and without neutrophil depletion

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Neutrophil depletion experiment in ischemia reperfusion mouse model

Project description:To elucidate the role of neutrophils in the molecular alterations observed after I/R, we performed an experiment of I/R in neutrophil-depleted mice. Neutrophil depletion was performed by anti-Ly6G injection and IgG was used as vehicle. We have performed an unbiased, open-search analysis of the oxidative PTMs and quantitative multiplexed proteomics that take place in the mouse heart tissue at 24h after I/R. Neutrophil depletion was performed in 3 mice by Ly6G injection 24h and 48 h prior to I/R and sacrificed 24 hours after reperfusion. A second group consisting on 3 mice that were injected with IgG antibody as vehicle, and subjected to I/R and sacrificed 24h after reperfusion. A third group of 3 mice with no injection were also sacrificed 24h after reperfusion. 12 additional mice from the three previous groups were sacrificed without I/R intervention: control without injection (n=6), IgG injection (n=3) and Ly6G injection (n=3). Whole hearts tissue was collected for proteomics evaluation.

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Circadian transcriptional profile of tissues with and without neutrophil depletion

Project description:We previously reported that neutrophils infiltrate most tissues in a circadian fashion, as they clear out from the circulation (Casanova‑Acebes et al., 2018). In our current study we hypothesized that neutrophils are relevant contributors to the matrix of barrier tissues and that then their elimination should leave a temporal footprint in the circadian pattern of expression of matrix-associated genes. To answer this question, we generated a circadian transcriptional dataset from the bone marrow, lung, liver, intestine and skin in wild type and neutrophil-depleted animals. The anlysis of the circadian patern of matrix related genes obtained from this datasets indicates that their temporal expression patterns in the analysed tissues is disrupted following neutrophil depletion. This results directly implicate neutrophils in the circadian biology of the matrix organization in various tissues.

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Project description:Interrogating the tumor immune compartment generates new prognostic and treatment modalities. We used the poorly immunogenic oncogenic Kras driven mouse model of lung cancer, to challenge the predictive value of an immune signature, using a new algorithm called MegaClust. It highlighted a predominant negative impact of neutrophil infiltration on multiple immune populations. Human samples and depletion experiments in mice revealed that neutrophils promote tumor growth by altering angiogenesis, associated to increased PI3K/Akt/mTOR signaling in tumor cells and profound immunosubversion. Together with blood vessel spreading and normalization, neutrophil depletion was associated with T cell redistribution into tumor mass and sensitized tumors to anti-PD1 immunotherapy in this refractory model. Our observations illustrate a mechanism of immune exclusion protecting tumor cells from destruction that relies on neutrophil infiltration

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