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Transposon-triggered innate immune response confers cancer resistance to the blind mole rat [array]

ABSTRACT: Blind mole rats (BMRs) are small rodents, characterized by exceptionally long lifespan (> 21 years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). BMR cells and tissues express very low levels of DNA methyltransferase 1 (DNMT1). Upon cell hyperplasia, the BMR genome DNA loses methylation, resulting in activation of RTEs. Up-regulated RTEs form cytoplasmic RNA/DNA hybrids, which activate cGAS-STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and human. We propose that RTEs were coopted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of innate immune response. RTEs activation is a double-edged sword, serving as a tumor suppressor but in late life contributing to aging via induction of sterile inflammation.

ORGANISM(S): Rattus norvegicus Mus musculus Nannospalax ehrenbergi Homo sapiens

PROVIDER: GSE181732 | GEO | 2021/10/01

REPOSITORIES: GEO

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Transposon-triggered innate immune response confers cancer resistance to the blind mole rat [seq]

Project description:Blind mole rats (BMRs) are small rodents, characterized by exceptionally long lifespan (> 21 years) and resistance to both spontaneous and induced tumorigenesis. Here we report that cancer resistance in the BMR is mediated by retrotransposable elements (RTEs). BMR cells and tissues express very low levels of DNA methyltransferase 1 (DNMT1). Upon cell hyperplasia, the BMR genome DNA loses methylation, resulting in activation of RTEs. Up-regulated RTEs form cytoplasmic RNA/DNA hybrids, which activate cGAS-STING pathway to induce cell death. Although this mechanism is enhanced in the BMR, we show that it functions in mice and human. We propose that RTEs were coopted to serve as tumor suppressors that monitor cell proliferation and are activated in premalignant cells to trigger cell death via activation of innate immune response. RTEs activation is a double-edged sword, serving as a tumor suppressor but in late life contributing to aging via induction of sterile inflammation.

2021-09-09 | GSE181413 | GEO

A survival mechanism controlled by cadherins and Dlg1 polarity complex inhibits Fas cell death receptor signaling

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2018-09-20 | PXD009659 | Pride

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Defining the microglia transcriptome during disease progression in ALS transgenic mice

Project description:Purpose: We purified spinal cord microglia utilizing percoll gradients and magnetic beads, followed by transcriptome profiling (RNA-seq) to define microglia expression profiles against other neural, immune cell-types. We next observed how the microglial transcriptomes change during activation in the SOD1-G93A mouse model of motor neuron degeneration at 3 time points. We also compared these profiles with that induced by LPS injection. Results and conclusions: ALS microglia were found to differ substantially from those activated by LPS and from M1/M2 macrophages by comparison with published datasets. These ALS microglia showing substantial induction of a neurodegeneration-tailored phenotype, with induction of lysosomal, RNA splicing, and Alzheimer's disease pathway genes. Overall they express a mixture of neuroprotective and neurotoxic factors during activation in ALS mice, showing that neuro-immune activation in the spinal cord is a double-edged sword. We also detected the transcriptional nature of surface marker expression in microglia (CD11b, CD86, CD11c), and substantial T-cell microglia cross-talk using correlative microglia transcriptome/FACS analysis. 42 total RNA samples from purified spinal cord microglia were subjected to paired-end RNA-sequencing. Parallel flow cytometry data was collected from the same spinal cords.

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Defining the microglia transcriptome during disease progression in ALS transgenic mice

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2013-07-15 | GSE43366 | GEO

Stress-inducible gene Atf3 dictates a dichotomous macrophage activity in chemotherapy-enhanced lung colonization

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Transposon-triggered innate immune response confers cancer resistance to the blind mole rat

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

2021-09-09 | GSE181733 | GEO

Hypoxia transcriptome sequencing of blind mole rat (BMR, Spalax galili) and rat (Rattus norvegicus)

Project description:Deep sequencing of mRNA from Spalax galili and Rattus norvegicus Total RNAs were isolated from the brain of female BMRs under various oxygen concentrations (3%, 6%, 10%, 14%, and 21%) for 6 hours. We also got RNAs from the brain of rats under 6%, 10%, 14%, and 21% oxygen conditions.

2014-06-05 | E-GEOD-49485 | biostudies-arrayexpress

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