- Tohoku University researchers analyzed individual hematopoietic stem cells from mice of different ages, finding that aged cells activate two gene programs: one that preserves a highly immature stem-cell state and another that prepares the cells to produce platelets.
- The team used Geneformer AI model trained on approximately 30 million cells and further trained on about 160,000 young and aged blood stem cells to predict aging-related genes.
- AI identified 143 candidate genes, which were screened in the lab and narrowed down to a key regulatory factor called Pbx1.
- Increasing Pbx1 in young stem cells reproduced features of aged cells, with up to 73.3% of Pbx1-activated genes also increased in aged cells.
- Transplantation experiments showed reduced red blood cell production and increased platelet production, with Pbx1 suppressing another gene called Gata1.
- The findings were published in Science Advances on August 22, 2026.
- Aged blood stem cells are often described as cells that have lost function, but findings show they enter a different, stable state with their own tendencies.
- This research provides a clearer molecular framework for understanding why blood production becomes unbalanced with age, affecting everyone as they grow older.
- Future studies will determine whether the same mechanism operates in humans and whether it contributes to anemia, thrombosis, clonal hematopoiesis, or blood cancers.
Tohoku University researchers have leveraged AI to uncover the role of Pbx1 in the aging of blood stem cells. Their study, published in Science Advances, reveals that aged hematopoietic stem cells activate two gene programs: one maintaining an immature state and another promoting platelet production.1346
Using the AI model Geneformer, trained on data from approximately 30 million cells, the team identified 143 candidate genes linked to aging. They focused on Pbx1, which was found to be significantly associated with genes related to stem-cell immaturity and aging. Notably, increasing Pbx1 in young stem cells replicated features of aged cells, with 73.3% of genes activated by Pbx1 also elevated in aged stem cells.
The researchers observed that aged stem cells produce fewer red blood cells while increasing platelet production, suggesting that Pbx1 may suppress the gene Gata1, which is crucial for red blood cell development. Takubo stated, "Aged blood stem cells are often described simply as cells that have lost function, but our findings show that they aren't a weaker version. They just enter a different, stable state with their own tendencies."57
This research not only enhances the understanding of blood production imbalance with age but also opens avenues for future studies to explore whether similar mechanisms exist in humans, potentially linking them to conditions like anemia, thrombosis, and blood cancers.89
“The AI model Geneformer, trained on ~30 million cells, predicted 143 candidates that were screened to Pbx1. Increasing Pbx1 in young stem cells reproduced aged features, with up to 73.3% of its activated genes also elevated in aged cells, and suppressed Gata1 to reduce red blood cell production.”
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