Single-cell transcriptional profiling reveals a novel RAB13+ endothelial subpopulation and profibrotic mesenchymal cells in the aged human bone marrow

Cenzano, I.; Cocera, M.; Lopez Perez, A. R.; Campos-Dopazo, L.; Ruiz, J.; Sancho, I.; San Martin-Uriz, P.; Sarvide, S.; Aguirre-Ruiz, P.; Vilas-Zornoza, A.; Ripalda-Cemborain, P.; Alignani, D.; Lopez, A.; Minana Barrios, M.; Quilez Agreda, D.; Ye, J.; Lehmann, R.; Sudupe, L.; Abengozar-Muela, M.; Tamariz-Amador, L.-E.; MUINOS-LOPEZ, E.; Saez, B.; Tegner, J.; A. Calvo, I.; Gomez-Cabrero, D.; Prosper, F.

doi:10.1101/2025.01.28.635238

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bioRxiv · 10.1101/2025.01.28.635238

Single-cell transcriptional profiling reveals a novel RAB13+ endothelial subpopulation and profibrotic mesenchymal cells in the aged human bone marrow

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Abstract

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 stem 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. TeaserAging reshapes the bone marrow with emergence of RAB13+ endothelial cells and profibrotic stromal cells altering tissue function.

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Cenzano, I., Cocera, M., Lopez Perez, A. R., Campos-Dopazo, L., Ruiz, J., Sancho, I., San Martin-Uriz, P., Sarvide, S., Aguirre-Ruiz, P., Vilas-Zornoza, A., Ripalda-Cemborain, P., Alignani, D., Lopez, A., Minana Barrios, M., Quilez Agreda, D., Ye, J., Lehmann, R., Sudupe, L., Abengozar-Muela, M., Tamariz-Amador, L.-E., MUINOS-LOPEZ, E., Saez, B., Tegner, J., A. Calvo, I., Gomez-Cabrero, D., Prosper, F.. 2025-01-29. Single-cell transcriptional profiling reveals a novel RAB13+ endothelial subpopulation and profibrotic mesenchymal cells in the aged human bone marrow. https://doi.org/10.1101/2025.01.28.635238

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