Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow.

Haruhito Totani, Takayoshi Matsumura, Rui Yokomori, Terumasa Umemoto, Yuji Takihara, Chong Yang, Lee Hui Chua, Atsushi Watanabe, Takaomi Sanda, Toshio Suda

Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. · pubmed

Paper

Abstract

The aging of hematopoietic stem cells (HSCs) substantially 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. In addition, these HSCs retain a high regenerative capacity and remain in the aging bone marrow. Furthermore, we identified GPR183 as a distinct 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 understanding of HSC aging and provide additional perspectives on the assessment of aged HSCs, underscoring the importance of mitochondrial dynamics in aging.

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Research summary

Hematopoietic stem cells with high mitochondrial mass in aged bone marrow exhibit enhanced self-renewal capabilities. This research addresses the underlying mechanisms of aging in stem cells, which is crucial for understanding longevity and potential interventions in age-related decline.

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