By transferring hematopoietic stem cells at mouse age (HSCn age) to the environment of young mice (bone marrow), it was demonstrated that the pattern of gas cell generation was restored to the pattern of young hematopoietic stem cells. On the other hand, the work of aged HSCs did not recover in the place of young bone marrow. The epigenome (DNA methylation) of aged HSCs did not change significantly even in the young bone marrow replacement, and DNA methylation profiles were found to be a better index of the expression pattern of the age HSCs gene.
A research group led by Professor Atsushi Iwama at the Department of Stem Cell and Molecular Medicine, Institute of Medical Science, University of Tokyo (IMSUT) named these results the best in the world and was published in the Journal of Experimental Medicine (online) on 24 November.
The findings will contribute to the development of treatments for age-related blood diseases. “
Professor Atsushi Iwama, Principal Scientist, IMSUT
Focus on changes in age HSCs in posterior bone marrow
The research group examined whether regenerating HSCs would age in a bone marrow niche environment.
Tens of thousands of hematopoietic gas / progenitor cells collected from 20-month-old mice were injected into 8-week young mice without prediction as irradiation. After two months of follow-up, they collected bone marrow cells and performed flow cytometric analysis.
The research team also replanted 10-week young mouse HSCs for comparison. In addition, engraved age HSCs were broken down and RNA sequence analysis and DNA methylation analysis were performed.
They found that engrafted age HSCs were less able to produce hematopoietic cells than younger HSCs. They also showed that the differentiation of age HSCs into proliferative progenitor cells was consistently impaired even in the backbone of young bone marrow, and that the direction of the difference was biased. It has been found that the transfer of aged HSCs to a bone marrow niche does not improve stem cell activity.
A more detailed study may reveal ways that inevitably affect HSC function at age
Age studies focusing on HSCn were actively followed in mice using a bone marrow translocation model. However, the age-related effects of HSCs remain to be clarified.
Professor Iwama says as follows. “This study has a significant impact because it clarified the effect of aging on HSCn. Our results are expected to contribute to further clarification of the mechanism of aging in HSCn and understanding of pathogenic mechanisms of blood co. age-related diseases. “
Source:
Institute of Medical Science, University of Tokyo
Magazine Reference:
Kuribayashi, W., et al. (2020) Limited regeneration of old hematopoietic cells in young bone marrow niche. Journal of Experimental Medicine. doi.org/10.1084/jem.20192283.