This study provides a comprehensive molecular map of human hematopoietic stem cell (HSC) differentiation across various stages of life. By utilizing advanced single-cell proteo-transcriptomic sequencing, researchers identified four distinct trajectories for cell development that remain largely consistent as humans age. A key finding is the identification of CD273 (PD-L2) as a surface marker for a specific group of quiescent, immature stem cells. Beyond serving as a marker for dormancy, this protein allows stem cells to perform an immune-modulatory role by suppressing T-cell activation. While the fundamental pathways of blood cell creation are preserved over time, the research highlights that aging leads to an expansion of immature cells and a decrease in the efficiency of progenitor production. Ultimately, these findings offer a detailed roadmap of the earliest genetic shifts that govern how stem cells maintain themselves or choose to transform into specific blood lineages.

References:

• Komic H, Schmachtel T, Simoes C, et al. Continuous map of early hematopoietic stem cell differentiation across human lifetime[J]. Nature Communications, 2025, 16(1): 2287.