Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration

被引：615

作者：

Goessling, Wolfram ^{[1
,2
,3
]}

North, Trista E. ^{[1
,2
,3
]}

Loewer, Sabine ^{[2
,3
]}

Lord, Allegra M. ^{[2
,3
]}

Lee, Sang ^{[2
,4
]}

Stoick-Cooper, Cristi L. ^{[5
]}

Weidinger, Gilbert ^{[5
]}

Puder, Mark ^{[2
,4
]}

Daley, George Q. ^{[1
,2
,3
]}

Moon, Randall T. ^{[5
]}

Zon, Leonard I. ^{[1
,2
,3
]}

机构：

[1] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

[3] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA

[4] Childrens Hosp, Dept Surg, Boston, MA 02115 USA

[5] Univ Washington, Howard Hughes Med Inst, Inst Stem Cell & Regenerat Med, Sch Med, Seattle, WA 98195 USA

来源：

CELL | 2009年 / 136卷 / 06期

基金：

美国国家卫生研究院;

关键词：

FAMILIAL ADENOMATOUS POLYPOSIS; GLYCOGEN-SYNTHASE KINASE-3; BETA-CATENIN; WNT/BETA-CATENIN; COLON-CANCER; LONG-TERM; PROSTAGLANDIN E-2; GAMMA-CATENIN; ZEBRAFISH; PHOSPHORYLATION;

D O I：

10.1016/j.cell.2009.01.015

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：

Interactions between developmental signaling pathways govern the formation and function of stem cells. Prostaglandin (PG) E2 regulates vertebrate hematopoietic stem cells (HSC). Similarly, the Wnt signaling pathway controls HSC self-renewal and bone marrow repopulation. Here, we show that wnt reporter activity in zebrafish HSCs is responsive to PGE2 modulation, demonstrating a direct interaction in vivo. Inhibition of PGE2 synthesis blocked wnt-induced alterations in HSC formation. PGE2 modified the wnt signaling cascade at the level of beta-catenin degradation through cAMP/PKA-mediated stabilizing phosphorylation events. The PGE2/Wnt interaction regulated murine stem and progenitor populations in vitro in hematopoietic ES cell assays and in vivo following transplantation. The relationship between PGE2 and Wnt was also conserved during regeneration of other organ systems. Our work provides in vivo evidence that Wnt activation in stem cells requires PGE2, and suggests the PGE2/Wnt interaction is a master regulator of vertebrate regeneration and recovery.

引用

页码：1136 / 1147

页数：12

共 44 条

[1] Mining the Wnt pathway for cancer therapeutics [J].