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

被引：117

作者：

Haug, Jeffrey S. ^{[1
]}

He, Xi C. ^{[1
]}

Grindley, Justin C. ^{[1
]}

Wunderlich, Joshua P. ^{[1
]}

Gaudenz, Karin ^{[1
]}

Ross, Jason T. ^{[1
]}

Paulson, Ariel ^{[1
]}

Wagner, Kathryn P. ^{[1
]}

Xie, Yucai ^{[1
]}

Zhu, Ruihong ^{[1
]}

Yin, Tong ^{[1
]}

Perry, John M. ^{[1
]}

Hembree, Mark J. ^{[1
]}

Redenbaugh, Erin P. ^{[1
]}

Radice, Glenn L. ^{[2
]}

Seidel, Christopher ^{[1
]}

Li, Linheng ^{[1
,3
]}

机构：

[1] Stowers Inst Med Res, Kansas City, MO 64110 USA

[2] Univ Penn, Sch Med, Ctr Res Reprod & Womens Hlth, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA

[3] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA

来源：

CELL STEM CELL | 2008年 / 2卷 / 04期

关键词：

D O I：

10.1016/j.stem.2008.01.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：367 / 379

页数：13

共 41 条

[1] Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis [J].