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Human immature neutrophils as a functional biomarker of systemic vascular pathologies

ABSTRACT: We used an ex vivo system of murine ER-Hoxb8 neutrophils that phenotypically and morphologically recapitulate neutrophil maturation stages during five days of in vitro culture in the presence of G-CSF. To investigate the development of the ROS system in neutrophils during their development, we compared transcriptomes of D0, D1, D3 and D5 Hoxb8 neutrophils.

ORGANISM(S): Mus musculus

PROVIDER: GSE147910 | GEO | 2020/09/15

REPOSITORIES: GEO

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Project description:Longevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions. These changes cause a transcriptome-wide loss in mRNA stoichiometry and loss of co-expression patterns in aging animals, as compared to young adults. Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality. In this study set out to measure aging in the transcriptome by determining drift-variance changes with age in C.elegans. We set up three different cohorts of water or mianserin treated animals. The title of each cohort indicates the treatment (e.g. h2o or mia), the concentration (mia2, mia10, mia50), the day when the treatment was started (e.g. d1= day 1 of adulthood) and the day when the sample was collected (e.g. d10= day 10 of adulthood). cohort #1: Celegans was treated with water or mianserin (50uM) on day 1 and RNA was harvested on day1 (water only), d3, d5 and day 10 (file titles: h2o d1/d1, h2o d1/d3, h2o d1/d5, h2o d1/d10, mia50 d1/d3, mia50 d1/d5, mia50 d1/d10) cohort #2: Celegans was treated with mianserin (50uM) starting on day 3, and day 5, RNA was harvested on day 5 or 10 (file titles: mia50 d3/d10, mia50 d5/d10, mia50 d3/d5) cohort #3: Celegans was treated with mianserin 2 uM and 10 uM Mianserin on day 1 and Rna harvested on day 5 (file titles: mia2 d1/d5, mia10 d1/d5)

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Human immature neutrophils as a functional biomarker of systemic vascular pathologies

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