Heme oxygenase-1 deficiency leads to disrupted response to acute stress in stem cells and progenitors

被引：46

作者：

Cao, Yu-An

Wagers, Amy J. ^{[2
]}

Karsunky, Holger ^{[2
]}

Zhao, Hui

Reeves, Robert

Wong, Ronald J.

Stevenson, David K.

Weissman, Irving L. ^{[2
]}

Contag, Christopher H. ^{[1
,3
,4
]}

机构：

[1] Stanford Univ, Dept Pediat, Div Neonatal & Dev Med, Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

来源：

BLOOD | 2008年 / 112卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1182/blood-2007-12-127621

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

An effective response to extreme hematopoietic stress requires an extreme elevation in hematopoiesis and preservation of hematopoietic stem cells (HSCs). These diametrically opposed processes are likely to be regulated by genes that mediate cellular adaptation to physiologic stress. Herein, we show that heme oxygenase-1 (HO-1), the inducible isozyme of heme degradation, is a key regulator of these processes. Mice lacking one allele of HO-1 (HO-1(+/-)) showed accelerated hematopoietic recovery from myelotoxic injury, and HO-1(+/-) HSCs re-populated lethally irradiated recipients with more rapid kinetics. However, HO-1(+/-) HSCs were ineffective in radioprotection and serial repopulation of myeloablated recipients. Perturbations in key stem cell regulators were observed in HO-1(+/-) HSCs and hematopoietic progenitors (HPCs), which may explain the disrupted response of HO-1(+/-) HPCs and HPCs to acute stress. Control of stem cell stress response by HO-1 presents opportunities for metabolic manipulation of stem cell based therapies. (Blood. 2008;112:4494-4502)

引用

页码：4494 / 4502

页数：9

共 33 条

[1]

MOLECULAR REGULATION - BIOLOGICAL ROLE OF HEME IN HEMATOPOIESIS [J].