RT Journal Article
SR Electronic
T1 Multi-omic profiling of primary mouse neutrophils reveals a pattern of sex and age-related functional regulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.06.190595
DO 10.1101/2020.07.06.190595
A1 Ryan Lu
A1 Shalina Taylor
A1 Kévin Contrepois
A1 Mathew Ellenberger
A1 Nirmal K. Sampathkumar
A1 Bérénice A. Benayoun
YR 2020
UL http://biorxiv.org/content/early/2020/07/06/2020.07.06.190595.abstract
AB Neutrophils are the most abundant white blood cells in humans and constitute one of the first lines of defense in the innate immune response. Neutrophils are extremely short-lived cells, which survive less than a day after reaching terminal differentiation. Thus, little is known about how organismal aging, rather than the daily cellular aging process, may impact neutrophil biology. In addition, accumulating evidence suggests that both immunity and organismal aging are sex-dimorphic. Here, we describe a multi-omic resource of mouse primary bone marrow neutrophils from young and old female and male mice, at the transcriptomic, metabolomic and lipidomic levels. Importantly, we identify widespread age-related and sex-dimorphic regulation of ‘omics’ in neutrophils, specifically regulation of chromatin. Using machine-learning, we identify candidate molecular drivers of age-related and sex-dimorphic transcriptional regulation of neutrophils. We leverage our resource to predict increased levels/release of neutrophil elastase in male mice. To date, this dataset represents the largest multi-omics resource for the study of neutrophils across biological sex and ages. This resource identifies molecular states linked to neutrophil characteristics linked to organismal age or sex, which could be targeted to improve immune responses across individuals.Competing Interest StatementThe authors have declared no competing interest.