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
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Cell Stem Cell. 2008 Apr 10;2(4):367-79. doi: 10.1016/j.stem.2008.01.017.
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.
表达同源性粘附分子N-钙粘蛋白的成骨细胞形成造血干细胞（HSC）龛位。因此，我们研究了造血干细胞中N-钙粘蛋白的表达与其功能之间的关系。我们发现，高表达N-钙粘蛋白（N-cadherin(hi)）的骨髓（BM）细胞不是干细胞，它们基本上缺乏谱系（Lineage）阴性、干细胞抗原1（Sca1）阳性、干细胞因子受体（cKit）阳性的细胞群体，并且无法在受辐照的受体小鼠中重建造血谱系。相反，长期造血干细胞形成了表达中等水平（N-cadherin(int)）或低水平（N-cadherin(lo)）N-钙粘蛋白的不同群体。少数N-cadherin(lo)群体能够有力地重建造血系统，表达可能促使它们动员的基因，并且在从骨髓动员到脾脏的造血干细胞中占主导地位。较大的N-cadherin(int)群体在刚分离时的重建试验中表现不佳，但在过夜体外培养后反应有所改善。它们的表达谱和较低的细胞周期进入率表明N-cadherin(int)细胞处于储备状态。因此，N-钙粘蛋白的差异表达反映了两个造血干细胞亚群之间的功能差异。
