Discovering The Aging Mechanism Of Blood Cell Forming Process

When the aged hematopoietic stem cells of mouse were transferred into the bone marrow of young mouse, a change in the stem cell expression to that of young hematopoietic stem cells was seen.

Hematopoietic stem cells (HSCs) are present in the bone marrow that forms other blood cells like white blood cells (WBCs), and platelets. By transferring the mouse aged hematopoietic stem cells to the bone marrow of the young mouse, the pattern of stem cell gene expression was rejuvenated to that of young hematopoietic stem cells.

However, the function of the aged HSCs did not recover in the young bone marrow. DNA methylation of aged HSCs, which is better than the gene expression pattern of aged HSCs, did not show significant change in the young bone marrow.

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‘When the aged hematopoietic stem cells of mouse were transferred into the bone marrow of young mouse, a change in the stem cell expression to that of young hematopoietic stem cells was seen.’
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The study led by Professor Atsushi Iwama at the Division of Stem Cell and Molecular Medicine, The Institute of Medical Science, The University of Tokyo (IMSUT) is published in the Journal of Experimental Medicine

The results of this study will contribute to the development of treatments for age-related blood diseases.

Changes In The Aged HSCs

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To investigate whether aged HSCs can be rejuvenated in a young bone marrow, tens of thousands of aged HSCs were collected from 20-month-old-mice and transplanted into 8-week old young mice. No pre-treatments like irradiation were given.,br>
The bone marrow cells were collected after 2 months of follow-up and flow cytometric analysis was performed.

For comparison, the team also transplanted 10-week-old young mouse HSCs. Along with this, engrafted aged HSCs were fractionated and DNA methylation and RNA sequence analysis were performed.

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The researchers found that the engrafted aged HSCs were less capable of producing hematopoietic cells than younger HSCs. It was also found that the differentiation of aged HSCs into multipotent progenitor cells was impaired even in the young bone marrow. The direction of differentiation was also biased.

The study showed that the transfer of aged HSCs to the young bone marrow does not improve their stem cell function.

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Many aging studies have focused on HSCs in mice by using a bone marrow transfer model. However the effect of aging on HSCs is still unclear.

Professor Iwama said, "This study has a significant impact because it clarified the effect of aging on HSCs. 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."

Source-Medindia