Decoding heterogeneity in hematopoietic aging

Le October 20 2026 at 09h00 Séminaire

Organismal aging arises from complex genetic and environmental interactions, making its mechanisms difficult to dissect. To minimize these variables, we profiled hematopoiesis in a large cohort of young and aged inbred female C57BL/6J mice housed under identical conditions, assessing blood, bone marrow, spleen, and transplantation phenotypes. Aged mice recapitulated expected hematopoietic aging features but showed striking inter-individual heterogeneity: some retained youthful traits, while others displayed pronounced age-associated changes. Even within individuals, canonical aging phenotypes varied independently, suggesting that hematopoietic aging does not follow a single trajectory. Using bone marrow single-cell RNA-seq, we generated cell type-specific aging scores and found broad transcriptomic variability among aged mice. Intercellular communication analysis linked distinct aging phenotypes to inflammatory signaling axes in the bone marrow niche. Neutrophil-derived Oncostatin M was associated with remodeling of the AdipoCAR-HSC niche axis and myeloid bias, whereas neutrophil-to-AdipoCAR IL-1 signaling correlated with anemia. These findings indicate that hematopoietic aging proceeds through multiple independent routes shaped by distinct inflammatory cell-cell communication programs within the bone marrow.