Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance.
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-cadherin(fl/-) 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.
Kiel
Mark J
MJ
Howard Hughes Medical Institute, Department of Internal Medicine, and Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109-2216, USA.
Acar
Melih
M
Radice
Glenn L
GL
Morrison
Sean J
SJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011839:Radiation, Ionizing; D033581:Stem Cell Transplantation
D015820:Cadherins; C489083:Cdh2 protein, mouse