@article{8770ca1b2ba8424491b48cb492f0976b,
title = "Lack of Evidence that Hematopoietic Stem Cells Depend on N-Cadherin-Mediated Adhesion to Osteoblasts for Their Maintenance",
abstract = "Recent studies have proposed that bone marrow hematopoietic stem cells (HSCs) are maintained via N-cadherin-mediated homophilic adhesion with osteoblasts. However, there is not yet any evidence that N-cadherin-expressing cells have HSC activity or that osteoblasts are required for HSC maintenance. We were unable to detect N-cadherin expression in highly purified HSCs by polymerase chain reaction, by using commercial anti-N-cadherin antibodies, or by β-galactosidase staining of N-cadherin gene trap mice. Only N-cadherin-negative bone marrow cells exhibited HSC activity in irradiated mice. Finally, biglycan-deficient mice had significant reductions in trabecular bone and osteoblasts but showed no defects in hematopoiesis, HSC frequency, or function. Thus, reductions in osteoblasts do not necessarily lead to reductions in HSCs. Most bone marrow HSCs in wild-type and biglycan-deficient mice localized to sinusoids, and few localized within five cell diameters of the endosteum. These results question whether significant numbers of HSCs depend on N-cadherin-mediated adhesion to osteoblasts.",
keywords = "STEMCELL",
author = "Kiel, {Mark J.} and Radice, {Glenn L.} and Morrison, {Sean J.}",
note = "Funding Information: This work was supported by the Howard Hughes Medical Institute and the U.S. Army Research Office (DAAD19-03-1-0168). M.J.K. was supported by a fellowship from the University of Michigan (UM) Cancer Biology program. Thanks to Lexicon Genetics for providing the N-cadherin lacZ gene trap mice, to Marian Young for providing biglycan-deficient mice, and to Larry Fisher for providing anti-Biglycan antiserum. Thanks to David Adams, Martin White, and the UM Flow Cytometry Core. Flow cytometry was supported in part by the UM Comprehensive Cancer, National Institutes of Health (NIH) CA46592. Thanks to Elizabeth Smith (Hybridoma Core Facility) for antibody production, supported in part through the Rheumatic Core Disease Center (P30 AR48310). M.J.K. performed all experiments and participated in the design and interpretation of experiments. G.L.R. suggested methods for detecting N-cadherin expression and provided the N-cadherin lacZ gene trap mice (originally made by Lexicon Genetics). S.J.M. participated in the design and interpretation of experiments and wrote the paper with M.J.K. ",
year = "2007",
month = aug,
day = "16",
doi = "10.1016/j.stem.2007.06.001",
language = "English (US)",
volume = "1",
pages = "204--217",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}