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Researchers discover aging mechanism for hematopoietic stem cells

TOKYO (JP), December 2020 — Researchers have demonstrated how transferring hematopoietic stem cells (HSCs) from aged mice into the bone marrow niche of young mice rejuvenates their stem cell gene expression to that of young hematopoietic stem cells. However, the function of the aged HSCs did not recover in the young bone marrow niche, the researchers said.

These results should contribute to the development of treatments for age-related blood diseases,

Additionally, the researchers, led by Atsushi Iwama, M.D., Ph.D., at the Division of Stem Cell and Molecular Medicine, Institute of Medical Science, University of Tokyo (IMSUT), found that the epigenome (DNA methylation) of the aged HSCs did not change significantly, even in the young bone marrow niche, and DNA methylation profiles were found to be a better index than the gene expression pattern of aged HSCs.

To conduct their study, the team collected tens of thousands of aged hematopoietic stem/progenitor cells from 20-month-old mice and transplanted them into 8-week-old young mice without pretreatment such as irradiation. After two months of follow-up, they collected bone marrow cells and performed flow cytometric analysis. The team also transplanted 10-week-old young mouse HSCs for comparison. In addition, engrafted aged HSCs were fractionated and RNA sequence analysis and DNA methylation analysis were performed.

Results showed that engrafted aged HSCs were less capable of producing hematopoietic cells than younger HSCs. The team also learned that differentiation of aged HSCs into multipotent progenitor cells was persistently impaired, even in the young bone marrow niche, and that the direction of differentiation was biased. The transfer of aged HSCs to the young bone marrow niche did not improve their stem cell function.

"This study has a significant impact because it clarified the effect of aging on HSCs,” Professor Iwama said. “Our results are expected to contribute to further elucidation of the mechanism of aging in HSCs and understanding of the pathogenic mechanism of age-related blood diseases."

The results of the study were published online Nov. 24 in the Journal of Experimental Medicine. 





Image courtesy of IMSUT.


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DOI: 10.1084/jem.20192283