Hematopoietic Stem Cell Development Is Dependent on Blood Flow

被引：356

作者：

North, Trista E. ^{[1
,2
]}

Goessling, Wolfram ^{[1
,3
,4
,5
]}

Peeters, Marian ^{[6
]}

Li, Pulin ^{[1
]}

Ceol, Craig ^{[1
]}

Lord, Allegra M. ^{[1
]}

Weber, Gerhard J. ^{[1
]}

Harris, James ^{[2
]}

Cutting, Claire C. ^{[3
]}

Huang, Paul ^{[7
]}

Dzierzak, Elaine ^{[6
]}

Zon, Leonard I. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Stem Cell Program & Hematol Oncol, Childrens Hosp,Howard Hughes Med Inst,Harvard Ste, Boston, MA 02115 USA

[2] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Erasmus MC, Erasmus Stem Cell Inst, NL-3000 DR Rotterdam, Netherlands

[7] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

来源：

CELL | 2009年 / 137卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NITRIC-OXIDE SYNTHASE; BETA-CATENIN; MOUSE; EXPRESSION; GENE; DISRUPTION; MIGRATION; EMBRYO; DIFFERENTIATION; ACTIVATION;

D O I：

10.1016/j.cell.2009.04.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

During vertebrate embryogenesis, hematopoietic stem cells (HSCs) arise in the aorta-gonads-mesonephros (AGM) region. We report here that blood flow is a conserved regulator of HSC formation. In zebrafish, chemical blood flow modulators regulated HSC development, and silent heart (sih) embryos, lacking a heartbeat and blood circulation, exhibited severely reduced HSCs. Flow-modifying compounds primarily affected HSC induction after the onset of heartbeat; however, nitric oxide (NO) donors regulated HSC number even when treatment occurred before the initiation of circulation, and rescued HSCs in sih mutants. Morpholino knockdown of nos1 (nnos/enos) blocked HSC development, and its requirement was shown to be cell autonomous. In the mouse, Nos3 (eNos) was expressed in HSCs in the AGM. Intrauterine Nos inhibition or embryonic Nos3 deficiency resulted in a reduction of hematopoietic clusters and transplantable murine HSCs. This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development.

引用

页码：736 / 748

页数：13

共 51 条

[1] Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells [J].