Single-cell 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.; Aguirre-Ruiz, P.; Sarvide, S.; 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.
Show 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.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A New Gene Set Identifies Senescent Cells and Predicts Senescence-Associated Pathways Across Tissues 96%
- Single Cell Transcriptomics of Fibrotic Lungs Unveils Aging-associated Alterations in Endothelial and Epithelial Cell Regeneration 96%
- Effect of Aging on the Human Myometrium at Single-Cell Resolution 96%
Similar papers in this journal
- Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single cell resolution 96%
- Mesenchymal Stromal Cell Aging Impairs the Self-Organizing Capacity of Lung Alveolar Epithelial Stem Cells 95%
- Impaired iron recycling from erythrocytes is an early iron-dependent hallmark of aging 95%
Similar papers in this journal
- The immune landscape of murine skeletal muscle regeneration and aging 97%
- Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging and inflammation 96%
- Multi-modal single cell analysis reveals brain immune landscape plasticity during aging and gut microbiota dysbiosis 94%
Similar papers in this journal
- Transcriptional activation of Jun and Fos members of the AP-1 complex is a conserved signature of immune aging that contributes to inflammaging 96%
- Single-cell RNA sequencing identifies accumulation of Fcgr2b+ virtual memory like CD8 T cells with cytotoxic and inflammatory potential in aged mouse white adipose tissue 95%
- Conclusive Identification of Senescent T Cells Reveals Their Abundance in Aging Humans 95%
Similar papers in this journal
- Disturbing immune homeostasis by neutrophil loss of Uba1 induces VEXAS-like autoinflammatory disease in mice 93%
- Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity and Inflammation in Myeloproliferative Neoplasms 93%
- An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.