Abstract

Circadian Rhythm Modulates the Ability of Pulmonary-derived Extracellular Vesicles to Alter Target Marrow Cell Phenotype

Laura Goldberg, Assistant Professor of Medicine, Brown University/Rhode Island Hospital

We are interested in how circadian rhythm influences extracellular vesicle (EV)-mediated inter-cellular communication.  To begin exploring whether circadian oscillations alter EV function, we employed a well-established in vitro system in which lung-derived EVs, when co-cultured with murine bone marrow cells, induce the bone marrow cells to express pulmonary epithelial cell-specific mRNA and protein. Using this readily manipulated in vitro system, we were able to vary the circadian time-point of both the lung harvest for EVs and the bone marrow cell harvest for target marrow cells prior to co-culture. We found that 1) EVs, when harvested from lung at distinct circadian time-points, differentially altered the expression of pulmonary epithelial specific mRNAs in target bone marrow cells in culture, and 2) altering the circadian time-point of the target whole bone marrow cells, and co-culturing with lung-derived EVs similarly resulted in statistically significant differences in pulmonary epithelial mRNA expression due to circadian oscillations of the recipient marrow cells. These data indicate that circadian rhythm is likely an important component of EV-mediated inter-cellular communication. Our ongoing work is aimed at elucidating the mechanisms by which circadian rhythm influences EV-mediated communication with bone marrow cells. We hope such studies will provide insight into the molecular mechanisms by which EVs alter the mRNA expression profile of target WBM and help optimize EV manipulations for therapeutic interventions in the future.