N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells
N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells
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DOI：
10.1016/j.stem.2008.01.017
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发表时间：
2008-04-01
期刊：
影响因子：
23.9
通讯作者：
Li, Linheng
中科院分区：
文献类型：
--
作者：
Haug, Jeffrey S.;He, Xi C.;Li, Linheng
表达同嗜性黏附分子N -钙黏蛋白的成骨细胞形成造血干细胞（HSC）微环境。因此，我们研究了HSCs中N -钙黏蛋白的表达与其功能之间的关系。我们发现高表达N -钙黏蛋白（N -钙黏蛋白hi）的骨髓（BM）细胞不是干细胞，其很大程度上缺乏谱系（-）Sca - 1（+）c - Kit（+）细胞群，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以中等（N -钙黏蛋白int）或低（N -钙黏蛋白lo）水平表达N -钙黏蛋白的不同细胞群。少数的N -钙黏蛋白lo细胞群能够有力地重建造血系统，表达可能使其易于动员的基因，并且在从骨髓动员到脾脏的HSCs中占主导地位。较大的N -钙黏蛋白int细胞群在新鲜分离时在重建实验中表现不佳，但经过一夜的体外培养后有所改善。它们的表达谱和较低的细胞周期进入率表明N -钙黏蛋白int细胞处于储备状态。因此，N -钙黏蛋白的差异表达反映了两个HSC亚群之间的功能差异。
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(-)Scal(+)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-cadherinint cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations.