Hematopoietic Stem Cells Do Not Depend on N-Cadherin to Regulate Their Maintenance

Abstract

SUMMARY According to the “osteoblastic niche” model, hematopoietic stem cells (HSCs) are maintained by N-cadherin-mediated homophilic adhesion to osteoblasts at the bone marrow endosteum. In contrast to this model, we cannot detect N-cadherin expression by HSCs and most HSCs do not localize to the endosteal surface. It has nonetheless been suggested that HSCs express low levels of N-cadherin that regulate HSC maintenance. To test this we conditionally deleted N-cadherin from HSCs and other hematopoietic cells in adult Mx-1-Cre+N-cadherinfl/− mice. N-cadherin deficiency had no detectable effect on HSC maintenance or hematopoiesis. N-cadherin deficiency did not affect bone marrow cellularity or lineage composition, the numbers of colony-forming progenitors, the frequency of HSCs, the ability of HSCs to sustain hematopoiesis over time, or their ability to reconstitute irradiated mice in primary or secondary transplants. Loss of N-cadherin does not lead to HSC depletion. N-cadherin expression by HSCs is not necessary for niche function.