Age-dependent and niche-specific variations in extracellular vesicle composition differentially modulate hematopoietic stem and progenitor cells
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Authors
Grenier-Pleau, Isabelle
Date
2024-09-19
Type
thesis
Language
eng
Keyword
extracellular vesicles , blood , aging , hematopoietic niche , hematopoietic stem and progenitor cells , quiescence , multi-omics , single-cell RNA sequencing
Alternative Title
Abstract
Hematopoietic stem cells (HSCs) are essential for lifelong blood production, uniquely capable of both self-renewal and differentiation into all blood cell lineages, adapting to the hematopoietic need of the organism. HSCs rely on intricate communication within the bone marrow microenvironment to govern their fate. While the influence of local niche factors is well known, the role of circulating factors, particularly extracellular vesicles (EVs), in HSC regulation during aging remains poorly understood. This thesis investigates the impact of EVs derived from distinct hematopoietic niches – peripheral blood plasma, bone marrow, and trabecular bone – on HSC quiescence, self-renewal, and differentiation, with a focus on age-related changes. We demonstrate that plasma-derived EVs exhibit age-associated alterations in their characteristics and functional impact on hematopoietic stem and progenitor cells (HSPCs). Notably, EVs enriched from the blood plasma of older individuals negatively impacted specific HSPC subpopulations, leading to increased mitochondrial dysfunction, DNA damage, and impaired DNA repair mechanisms – effects absent in those exposed to EVs from younger individuals. Further emphasizing the influence of EV source, our findings reveal that EVs define distinct microenvironments within the hematopoietic system, with trabecular bone-derived EVs playing a unique role in maintaining HSC quiescence. This research highlights the intricate interplay between age, niche-specific EVs, and HSC fate, emphasizing the importance of understanding EV-mediated communication within the bone marrow microenvironment for developing novel therapeutic strategies targeting age-related hematopoietic decline and diseases.
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Attribution-NonCommercial-NoDerivatives 4.0 International
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.