N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells

Osteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherin(hi)) are not stem cells, be...

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Published in:Cell stem cell 2008-04, Vol.2 (4), p.367-379
Main Authors: Haug, Jeffrey S, He, Xi C, Grindley, Justin C, Wunderlich, Joshua P, Gaudenz, Karin, Ross, Jason T, Paulson, Ariel, Wagner, Kathryn P, Xie, Yucai, Zhu, Ruihong, Yin, Tong, Perry, John M, Hembree, Mark J, Redenbaugh, Erin P, Radice, Glenn L, Seidel, Christopher, Li, Linheng
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Language:English
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Summary:Osteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherin(hi)) are not stem cells, being largely devoid of a Lineage(-)Sca1(+)cKit(+) population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherin(int)) or low (N-cadherin(lo)) levels. The minority N-cadherin(lo) population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherin(int) population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherin(int) cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations.
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2008.01.017