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

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

  • Nat Aging. 2025 Mar 6. doi: 10.1038/s43587-025-00828-y.
Haruhito Totani # 1,  Takayoshi Matsumura # 2 3,  Rui Yokomori 1,  Terumasa Umemoto 4,  Yuji Takihara 1,  Chong Yang 1 5,  Lee Hui Chua 1,  Atsushi Watanabe 1,  Takaomi Sanda 1 6,  Toshio Suda 7 8 9
Affiliations

Affiliations

  • 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • 2 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. matsut@jichi.ac.jp.
  • 3 Division of Cardiovascular and Genetic Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan. matsut@jichi.ac.jp.
  • 4 International Research Center of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • 5 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
  • 6 Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • 7 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. sudato@keio.jp.
  • 8 International Research Center of Medical Sciences, Kumamoto University, Kumamoto, Japan. sudato@keio.jp.
  • 9 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. sudato@keio.jp.
  • # Contributed equally.
PMID: 40050412 DOI: 10.1038/s43587-025-00828-y
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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