AI Identifies Key Gene Driving Hematopoietic Stem Cell Aging

Key Points

• AI analysis identified Pbx1 as a potential regulator of hematopoietic stem cell aging.
• Aged blood stem cells showed increased programs linked to stem-cell immaturity and platelet production.
• Pbx1 altered young stem cells to resemble aged cells and reduced red blood cell production after transplantation.
• The findings may help clarify mechanisms behind anemia, thrombosis, clonal hematopoiesis, and blood disorders.

What Drives Hematopoietic Stem Cell Aging?

Hematopoietic stem cell aging may involve a shift into a stable cellular state rather than simply a loss of function, according to research from Tohoku University published in Science Advances on August 22, 2026.

Hematopoietic stem cells in bone marrow continuously generate red blood cells, white blood cells, and platelets throughout life. With aging, their numbers increase, but their capacity to rebuild the blood system declines. This imbalance may contribute to anemia, impaired immunity, thrombosis, and age-related hematologic disorders.

Researchers analyzed individual hematopoietic stem cells from young and aged mice and identified two gene programs that become active during aging. One maintained an immature stem-cell state, while the other promoted platelet production. The gradual activation of these programs suggested that stem cell aging develops continuously rather than appearing abruptly in later life.

How Did AI Identify Pbx1 as a Driver of Hematopoietic Stem Cell Aging?

The research team used Geneformer, an AI model trained on gene-expression information from approximately 30 million cells. They further trained the model using data from about 160,000 young and aged blood stem and progenitor cells.

The AI analysis identified 143 candidate genes that could influence the transition toward an aged stem-cell state. Laboratory screening narrowed these candidates to Pbx1, a gene-regulating factor strongly associated with aging-related cellular programs.

Increasing Pbx1 in young stem cells reproduced several characteristics observed in aged cells. Up to 73.3% of genes activated by Pbx1 were also increased in aged stem cells. Following transplantation into mice, Pbx1-enhanced cells generated fewer red blood cells while showing relatively greater platelet production.

The researchers proposed that Pbx1 may contribute to reduced red blood cell development by suppressing Gata1, a gene involved in blood-cell differentiation.

What Could Pbx1 Mean for Age-Related Blood Disorders?

The findings provide a molecular framework for understanding how hematopoietic stem cells change with age. Rather than functioning as simply weaker versions of young cells, aged stem cells may adopt a distinct and stable biological state with specific blood-production tendencies.

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For hematologists, oncologists, researchers, and other healthcare professionals, understanding this regulatory pathway could help clarify mechanisms associated with anemia, thrombosis, clonal hematopoiesis, and blood cancers.

The study combined AI-based prediction, large-scale genetic screening, multi-omics analysis, and transplantation experiments. Future research will need to establish whether the same Pbx1-associated mechanism occurs in human hematopoietic stem cells and determine its relevance to age-related hematologic disease.

For HCPs: These findings highlight how AI-driven analysis of cellular data can help identify molecular regulators of hematopoietic stem cell aging and generate targets for further translational research.

Source:

Tohoku University