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Single-cell profiling uncovers transcriptional shifts in endothelial and mesenchymal cells in aged humans, suggesting new targets for age-related issues.
The bone marrow (BM) microenvironment plays a crucial role in regulating hematopoiesis, yet the molecular changes associated with aging in humans remain poorly understood. Using single-cell RNA sequencing, we uncovered transcriptional shifts in BM endothelial cells (EC) and mesenchymal stromal cells (MSC) during aging. Aged sinusoidal EC exhibited a prothrombotic phenotype with compromised mitochondrial and vascular function. Additionally, we identified a novel arterial EC subset, emerging in aged individuals, characterized by RAB13 expression and associated with transcriptional regulatory processes. MSC from aged subjects displayed impaired matrix remodeling and epithelial-mesenchymal transition, driven partly by a subpopulation of THY1⁺ profibrotic cells absent in younger individuals. Finally, immunofluorescent imaging and spatial transcriptomics confirmed the presence of these aging-associated cells in BM samples from aged individuals. In summary, this work provides a comprehensive view of the transcriptional landscape, cellular interactions, and spatial organization of aged EC and MSC, offering novel insights and potential targets that could be exploited for preventing age-associated changes in humans.
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Cenzano et al. (2026) studied this question.
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