Septin 6 regulates engraftment and lymphoid differentiation potential of murine long-term hematopoietic stem cells.

Septins are a family of filament-forming GTP-binding proteins that serve as scaffolds and diffusion barriers in various cellular processes. Septin 6 is known as a fusion partner of mixed-lineage leukemia in infant acute myeloid leukemia. The occurrence of the fusion gene is associated with a reduced expression of septin 6 itself. The role of septin 6 in hematopoiesis and whether it is involved in scaffolds within hematopoietic cells is not known. Septin 6-deficient hematopoietic stem cells (HSCs) present with an increased engraftment potential but altered lymphoid differentiation with a reduced contribution to the T-cell compartment and an increased B-cell contribution. Although multipotent progenitor cells showed a very distinct septin 6 filament organization and intracellular distribution, their function was not impaired by septin 6 deficiency. Our data therefore suggest a regulatory role for septin 6 in long-term HSC function and lymphoid lineage differentiation.