Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance

Cell Stem Cell. 2009 Feb 6;4(2):170-9. doi: 10.1016/j.stem.2008.10.005.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Lineage
  • Cells, Cultured
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Radiation, Ionizing
  • Stem Cell Transplantation

Substances

  • Cadherins
  • Cdh2 protein, mouse