Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow [single cell multiome]

The aging of hematopoietic stem cells (HSCs) significantly alters their characteristics. Mitochondria, essential for cellular metabolism, play a crucial role, and their dysfunction is a hallmark of aging-induced changes. The impact of mitochondrial mass on aged HSCs remains incompletely understood. Here, we demonstrate that HSCs with high mitochondrial mass during aging are not merely cells that have accumulated damaged mitochondria and become exhausted. Instead, these HSCs retain a high regenerative capacity and remain in the aging bone marrow. Furthermore, we identified GPR183 as a novel marker characterizing aged HSCs through single-cell analysis. HSCs marked by GPR183 were also enriched in aged HSCs with high mitochondrial mass, possessing a high capacity of self-renewal. These insights deepen our understanding of HSC aging and provide new perspectives on the assessment of aged HSCs, underscoring the importance of mitochondrial dynamics in the aging. Overall design: Single cell mutiome analysis (single cell RNA-seq and single cell ATAC-seq) of young and aged mitoDendra2 Low and High HSCs