Research conducted by scientists from Baylor College of Medicine and the Wellcome Sanger Institute has unveiled significant differences in how blood stem cells evolve over a lifespan between humans and mice. Published in Nature, the study sheds light on factors influencing tissue ageing.
The research reveals that drastic changes observed in human blood during old age are not mirrored in mice. In humans, somatic mutations lead to significant changes in blood after age 70, with older individuals relying heavily on a reduced set of expanded stem cell clones for blood production. These clones can develop into cancer and other diseases.
The team investigated whether these patterns are universal across species by studying mouse blood stem cells' development over their lifespan. They sequenced the genomes of 1,305 mouse blood stem cells to identify mutations and reconstruct 'family trees' of blood production.
Findings showed that unlike humans, mice maintain diverse blood stem cells throughout life without collapsing into dominant clones. This may explain why age-related blood disorders are less common in older mice. Mice accumulate mutations at a lower rate than expected, suggesting special protection for their blood stem cells.
Interestingly, despite their smaller size and shorter lifespan, mice have around 70,000 blood stem cells compared to humans' 20,000 to 200,000. The researchers propose this might be an evolutionary adaptation for rapid environmental response.
In humans, key mutations driving clone expansion were also found in mice but at low levels insufficient to cause issues as seen in humans. Human healthy blood stem cells divide once or twice yearly; however, mouse counterparts divide every six weeks due to their shorter lifespan.
These differences imply that findings from mouse models cannot be directly applied to human biology without consideration. Dr Chiraag Kapadia stated: “Expansions of cells are a ubiquitous feature of ageing human tissue... Understanding how blood stem cells develop over time in species with a different lifespan to humans is invaluable knowledge.”
Professor Margaret Goodell added: “With this study, we now have a better understanding of how environmental exposures shape patterns of ageing through stem cell adaptation.” Dr Jyoti Nangalia noted: “This work gives us a more complete understanding of the factors that come together to determine how a tissue ages over an organism’s lifetime.”
The study provides new insights into using laboratory models for researching ageing and offers frameworks for interpreting findings involving mouse-derived data.
