RETRACTED: Notch1 regulates the fate of cardiac progenitor cells (Retracted Article)

被引：158

作者：

Boni, Alessandro ^{[1
,2
,3
]}

Urbanek, Konrad ^{[1
,2
,3
]}

Nascimbene, Angelo ^{[1
,2
,3
]}

Hosoda, Toru ^{[1
,2
,3
]}

Zheng, Hanqiao ^{[1
,2
,3
]}

Delucchi, Francesca ^{[1
,2
,3
]}

Amano, Katsuya ^{[1
,2
,3
]}

Gonzalez, Arantxa ^{[1
,2
,3
]}

Vitale, Serena ^{[1
,2
,3
]}

Ojaimi, Caroline ^{[4
]}

Rizzi, Roberto ^{[1
,2
,3
]}

Bolli, Roberto ^{[5
]}

Yutzey, Katherine E. ^{[6
]}

Rota, Marcello ^{[1
,2
,3
]}

Kajstura, Jan ^{[1
,2
,3
]}

Anversa, Piero ^{[1
,2
,3
]}

Leri, Annarosa ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA

[4] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA

[5] Univ Louisville, Inst Mol Cardiol, Louisville, KY 40292 USA

[6] Childrens Med Ctr, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 40期

基金：

美国国家卫生研究院;

关键词：

cardiac regeneration; myocardial infarction;

D O I：

10.1073/pnas.0808357105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Notch receptor mediates cell fate decision in multiple organs. in the current work we tested the hypothesis that Nkx2.5 is a target gene of Notch1 and raised the possibility that Notch1 regulates myocyte commitment in the adult heart. Cardiac progenitor cells (CPCs) in the niches express Notch1 receptor, and the supporting cells exhibit the Notch ligand Jagged1. The nuclear translocation of Notch1 intracellular domain (N1ICD) up-regulates Nkx2.5 in CPCs and promotes the formation of cycling myocytes in vitro. N1ICD and RBP-Jk form a protein complex, which in turn binds to the Nkx2.5 promoter initiating transcription and myocyte differentiation. In contrast, transcription factors of vascular cells are down-regulated by Jagged1 activation of the Notch1 pathway. Importantly, inhibition of Notch1 in infarcted mice impairs the commitment of resident CPCs to the myocyte lineage opposing cardiomyogenesis. These observations indicate that Notch1 favors the early specification of CPCs to the myocyte phenotype but maintains the newly formed cells in a highly proliferative state. Dividing Nkx2.5-positive myocytes correspond to transit amplifying cells, which condition the replicative capacity of the heart. In conclusion, Notch1 may have critical implications in the control of heart homeostasis and its adaptation to pathologic states.

引用

页码：15529 / 15534

页数：6

共 26 条

[1] Roles of cardiac transcription factors in cardiac hypertrophy [J].