Fetal gene Lin28b improves ex vivo expansion of aged mouse blood stem cells
Researchers found that boosting Lin28b expression during ex vivo culture restores the transplantation and reconstitution capacity of aged mouse hematopoietic stem cells.
Researchers studied hematopoietic stem cells from mouse fetal liver, young bone marrow, and aged bone marrow to examine how they expand outside the body. They discovered that ex vivo expansion activates Lin28b, a gene normally restricted to fetal development in vivo. Lin28b expression correlated with cell reconstitution potential after transplantation, showing high levels in expanded fetal and young adult cells. In contrast, expanded aged stem cells failed to express Lin28b robustly and failed to stably reconstitute the hematopoietic system. Cells lacking Lin28b acquired aging-associated functional and molecular defects during culture. Crucially, overexpressing Lin28b during expansion enhanced the reconstitution potential of aged stem cells.
Why it matters
The findings identify Lin28b as a critical regulator of blood stem cell expansion and suggest that re-engaging developmental programs could help rejuvenate aged stem cells for therapeutic use.
Caveats
The study was conducted entirely in mouse cells and ex vivo culture models, so it remains unknown whether these mechanisms operate similarly in human hematopoietic stem cells.
The paper
Adult hematopoietic stem cells activate a normally fetal-restricted program to functionally expand ex vivo
Igarashi KJ, Nicholls M, Olender L et al.
Blood · 1 Oct 2026