N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells - PubMed (original) (raw)

. 2008 Apr 10;2(4):367-79.

doi: 10.1016/j.stem.2008.01.017.

Xi C He, Justin C Grindley, Joshua P Wunderlich, Karin Gaudenz, Jason T Ross, Ariel Paulson, Kathryn P Wagner, Yucai Xie, Ruihong Zhu, Tong Yin, John M Perry, Mark J Hembree, Erin P Redenbaugh, Glenn L Radice, Christopher Seidel, Linheng Li

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

Jeffrey S Haug et al. Cell Stem Cell. 2008.

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Abstract

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.

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