2022•bioRxiv (Cold Spring Harbor Laboratory)Open access
Lipid Droplets Fuel Small Extracellular Vesicle Biogenesis
Géraldine C. Genard, Luca Tirinato, Francesca Pagliari, Jéssica Da Silva, Alessandro Giammona, Fatema Alquraish, Marie Bordas, Maria Grazia Marafioti, Simone Di Franco, Jeannette Janssen, Daniel García-Calderón, Rachel Hanley, Clelia Nisticò, Yoshinori Fukasawa, Torsten Müller, Jeroen Krijgsveld, Matilde Todaro, Francesco Saverio Costanzo, Giorgio Stassi, Michelle Neßling, Karsten Richter, Kendra K. Maaß, Carlo Liberale, Joao Carlos Seco
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Abstract
Abstract Despite an increasing gain of knowledge regarding small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we revealed for the first time that the sEV biogenesis and release into the microenvironment are tightly connected with another important organelle: Lipid Droplets (LD). We have observed this correlation using different human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results showed that the use of external stimuli such as radiation, pH, hypoxia, or lipid interfering drugs, known to affect the LD content, had a similar effect in terms of sEV secretion. Additional validations were brought using multiple omics data, at the mRNA and protein levels. Altogether, the possibility to fine-tune sEV biogenesis by targeting LDs, could have a massive impact on the amount, the cargos and the properties of those sEVs, paving the way for new clinical perspectives. Significance Statement
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