Septin7 is essential in early hematopoiesis, but redundant at later stages

Abstract

The unique cytoskeletal protein Septin7 is generally considered to be required for cytokinesis in yeast and mammals. Whole body genetic ablation of Septin7 in mice is embryonic lethal. Septin7-deficient fibroblasts and HeLa cells are defective in cytokinesis and undergo obligate multinucleation. Surprisingly, lymphocyte- and myeloid-specific deletion of Septin7 in mice did not result in any detectable abnormalities in blood lineage development, suggesting that Septin7 is dispensable for steady-state hematopoiesis. In contrast, Septin7-deficient hematopoietic stem cells failed to engraft and establish donor chimerism following transplantation, indicating that Septin7 is essential for hematopoietic stem cell function under stress conditions. To reconcile these contradictory findings, we analyzed the effects of Septin7 deletion in hematopoietic cells from mice with either pan-hematopoietic or lymphoid lineage-specific Septin7 deletion. Our results demonstrate that Cre-induced deletion of the floxed Septin7 allele is inefficient during the early stages of hematopoiesis, suggesting strong selection pressure against Septin7 deficiency at this stage. In contrast, deletion of Septin7 at the common lymphoid progenitor stage, as well as in Hoxb8-immortalized hematopoietic progenitors, is efficient and does not result in any noticeable defects in cell division. Taken together, our findings indicate that Septin7 is essential during early hematopoiesis but becomes dispensable at later stages.