Blood extracellular vesicles from healthy individuals regulate hematopoietic stem cells as humans age

Grenier-Pleau, Isabelle and Tyryshkin, Kathrin and Le, Tri Dung and Rudan, John and Bonneil, Eric and Thibault, Pierre and Zeng, Karen and Lässer, Cecilia and Mallinson, David and Lamprou, Dimitrios and Hui, Jialui and Postovit, Lynne-Marie and Chan, Edmond Y. W. and Abraham, Sheela A. (2020) Blood extracellular vesicles from healthy individuals regulate hematopoietic stem cells as humans age. Aging Cell, 19 (11). e13245. ISSN 1474-9726

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    Abstract

    Hematopoietic stem cells (HSCs) maintain balanced blood cell production in a process called hematopoiesis. As humans age, their HSCs acquire mutations that allow some HSCs to disproportionately contribute to normal blood production. This process, known as age-related clonal hematopoiesis, predisposes certain individuals to cancer, cardiovascular and pulmonary pathologies. There is a growing body of evidence suggesting that factors outside cells, such as extracellular vesicles (EVs), contribute to the disruption of stem cell homeostasis during aging. We have characterized blood EVs from humans and determined that they are remarkably consistent with respect to size, concentration, and total protein content, across healthy subjects aged 20–85 years. When analyzing EV protein composition from mass spectroscopy data, our machine-learning-based algorithms are able to distinguish EV proteins based on age and suggest that different cell types dominantly produce EVs released into the blood, which change over time. Importantly, our data show blood EVs from middle and older age groups (>40 years) significantly stimulate HSCs in contrast to untreated and EVs sourced from young subjects. Our study establishes for the first time that although EV particle size, concentration, and total protein content remain relatively consistent over an adult lifespan in humans, EV content evolves during aging and potentially influences HSC regulation.

    ORCID iDs

    Grenier-Pleau, Isabelle, Tyryshkin, Kathrin, Le, Tri Dung, Rudan, John, Bonneil, Eric, Thibault, Pierre, Zeng, Karen, Lässer, Cecilia, Mallinson, David ORCID logoORCID: https://orcid.org/0000-0003-2615-633X, Lamprou, Dimitrios, Hui, Jialui, Postovit, Lynne-Marie, Chan, Edmond Y. W. and Abraham, Sheela A.;