Stem cells: Valine starvation leads to a hungry niche

Abstract

The haematopoietic stem cells that rejuvenate blood depend on a dietary source of the amino acid valine — a finding that has been exploited to reduce the toxicity of bone-marrow transplantation in mice.

Figure 1. Reducing toxicity in bone-marrow transplantation

a, In conventional bone-marrow transplantation in mice, radiation is used to ablate haematopoietic stem cells (HSCs), but this treatment also damages the niche in which the HSCs grow in close proximity to small bone-marrow blood vessels called sinusoids. Healthy donor HSCs are then transplanted into the bone marrow, and completely reconstitute the blood. This approach is effective in replacing the recipient’s blood-forming system, but causes infertility and diminished lifespan. b, Taya et al. describe an alternative approach. Depletion of the amino acid valine from the diet causes a degree of native HSC depletion and dysfunction that enables the engraftment of healthy donor HSCs, while apparently preserving the niche. The engrafted HSCs partially contribute to the blood-forming system, and some recipient HSCs recover when mice are put back on a normal diet. Mice transplanted using this strategy have normal lifespans and fertility.