Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium

被引：130

作者：

Van Handel, Ben ^{[1
]}

Montel-Hagen, Amelie ^{[1
]}

Sasidharan, Rajkumar ^{[1
]}

Nakano, Haruko ^{[1
]}

Ferrari, Roberto ^{[2
]}

Boogerd, Cornelis J. ^{[8
,9
]}

Schredelseker, Johann ^{[1
]}

Wang, Yanling ^{[1
]}

Hunter, Sean ^{[1
]}

Org, Tonis ^{[1
]}

Zhou, Jian ^{[3
]}

Li, Xinmin ^{[3
]}

Pellegrini, Matteo ^{[1
,4
,5
,6
]}

Chen, Jau-Nian ^{[1
]}

Orkin, Stuart H. ^{[10
,11
,12
]}

Kurdistani, Siavash K. ^{[2
,4
,5
,6
]}

Evans, Sylvia M. ^{[8
,9
]}

Nakano, Atsushi ^{[1
,4
,5
,6
]}

Mikkola, Hanna K. A. ^{[1
,4
,5
,6
,7
]}

机构：

[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[8] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

[9] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[10] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[12] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

CELL | 2012年 / 150卷 / 03期

关键词：

HEMATOPOIETIC STEM-CELLS; AORTIC ENDOTHELIUM; PROGENITOR CELLS; CARDIOVASCULAR PROGENITORS; HAEMOGENIC ENDOTHELIUM; DEFINED FACTORS; SMOOTH-MUSCLE; MOUSE EMBRYO; DIFFERENTIATION; BLOOD;

D O I：

10.1016/j.cell.2012.06.026

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：

Endothelium in embryonic hematopoietic tissues generates hematopoietic stem/progenitor cells; however, it is unknown how its unique potential is specified. We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoietic transcriptional program in hemogenic endothelium and preventing its misspecification to a cardiomyogenic fate. Scl(-/-) embryos activated a cardiac transcriptional program in yolk sac endothelium, leading to the emergence of CD31(+)Pdgfr alpha(+) cardiogenic precursors that generated spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in Scl(-/-) hearts, where the disorganized endocardium precociously differentiated into cardiomyocytes. Induction of mosaic deletion of Scl in Scl(fl/fl)Rosa26Cre-ERT2 embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent cardiomyogenesis from endothelium. Scl(-/-) endothelium also upregulated the expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation of ectopic cardiogenic cells. These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells.

引用

页码：590 / 605

页数：16

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