Maude Lanoie’s bio
Maude is a graduate student in the Molecular Biology program at the Université de Montréal. She is also a trainee in the Canadian Donation and Transplantation Research program (CDTRP). Maude obtained her BSc degree in Biomedical Sciences at the Université de Montréal where she also completed a minor in Public Health. She joined Dr. Hébert’s lab in 2022 as a master’s student and is currently working on characterizing the mechanisms by which ApoExos load specific sets of nucleic acids to shape endothelial function. Outside of the lab, Maude plays rugby for the Carabins de l’Université de Montréal.
Apoptotic exosome-like vesicles transfer bioactive mRNA to endothelial cells via phosphatidylserine-dependent macropinocytosis
Alexandre Brodeur, Francis Migneault. Nicolas Thibodeau, Déborah Beillevaire, Mélanie Dieudé, Marie-Josée Hébert
When kidneys lack blood supply, because of renal transplantation, small vessels that bring oxygen and nutrients to the kidney become injured. The loss of microscopic blood vessels is a major factor in kidney dysfunction and chronic disease installation. Our group identified small fragments of vascular
cells called apoptotic exosomes that are released in the circulation when kidneys lack oxygen. These fragments can induce an immune response and a
modification of the blood vessel environment that may affect the transition from an acute kidney injury to the loss of the kidney transplant. We already
showed that apoptotic exosomes harbor some specific enzymes and RNA molecules known to induce the production of antibodies that can in turn further damage the kidneys. Here, we explore the mechanism by which vascular cells can internalize apoptotic exosomes and shape microscopic blood vessels. To do that, we exposed cells to apoptotic exosomes labeled with fluorescent molecules to track them once internalized. We used inhibitors and genetic techniques to assess the different entryways inside cells. We found that apoptotic exosomes are internalized in blood vessel cells by a non-classical mechanism and that they can promote their entry by activating this same mechanism. We showed that functional RNA molecules can be delivered to cells through apoptotic exosomes and impact the homeostasis of the recipient cells. We also discovered that blocking this entryway prevents the transfer of molecules from apoptotic exosomes to its surrounding and prevents the alteration of the vascular bed around injured vessels. These results open new avenues for preventing apoptotic exosome internalization and preventing the development of kidney dysfunction.