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

Abstract:

: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 repopulated 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.

journal_name

Blood

journal_title

Blood

authors

Cao YA,Wagers AJ,Karsunky H,Zhao H,Reeves R,Wong RJ,Stevenson DK,Weissman IL,Contag CH

doi

10.1182/blood-2007-12-127621

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

4494-502

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2007-12-127621

journal_volume

112

pub_type

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