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.
|
|