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

作者：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^*

来源：Cell Stem Cell, 2008, 2(4): 367-379.

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(-)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.

• 出版日期2008-4
• 单位河北医科大学