SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a.

SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Research Abstract Details 

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SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Abstract Text:

Arjun Deb,Bryce H Davis,Jian Guo,Aiguo Ni,Jing Huang,Zhiping Zhang,Hui Mu,Victor J Dzau,Arjun Deb,Bryce H Davis,Jian Guo,Aiguo Ni,Jing Huang,Zhiping Zhang,Hui Mu,Victor J Dzau,

Wnts comprise a family of 20 lipid-modified glycoproteins in mammals and play critical roles during embryological development and organogenesis of several organ systems, including the heart. They are required for mesoderm formation and have been implicated in promoting cardiomyogenic differentiation of mammalian embryonic stem cells, but the underlying mechanisms regulating Wnt signaling during cardiomyogenesis remain poorly understood. In this report, we show that in a pluripotent mouse embryonal carcinoma stem cell line, SFRP2 inhibits cardiomyogenic differentiation by regulating Wnt3a transcription. SFRP2 inhibited early stages of cardiomyogenesis, preventing mesoderm specification and maintaining the cells in the undifferentiated state. Using a gain- and loss-of-function approach, we demonstrate that although addition of recombinant SFRP2 decreased Wnt3a transcription and cardiomyogenic differentiation, silencing of Sfrp2 led to enhanced Wnt3a transcription, mesoderm formation, and increased cardiomyogenesis. We show that the inhibitory effects of SFRP2 on Wnt transcription are secondary to interruption of a positive feedback effect of Wnt3a on its own transcription. Wnt3a increased its own transcription via the canonical pathway and TCF4 family of transcription factors, and the inhibitory effects of SFRP2 on Wnt3a transcription were associated with disruption of downstream canonical Wnt signaling. The inhibitory effects of Sfrp2 on Wnt3a expression identify Sfrp2 as a "checkpoint gene," which exerts its control on cardiomyogenesis through regulation of Wnt3a transcription.

SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Publishing Authors By Initials

A Deb,BH Davis,J Guo,A Ni,J Huang,Z Zhang,H Mu,VJ Dzau,A Deb,BH Davis,J Guo,A Ni,J Huang,Z Zhang,H Mu,VJ Dzau,

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SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Stem cells (Dayton, Ohio)

VOLUME: 26

Page Numbers: 35-44

Journal Abbreviation: Stem Cells

ISSN: 1549-4918

DAY: 4

MONTH: 10

YEAR: 2007

SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Information

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LANGUAGE: eng

NlmUniqueID: 9304532

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AFFILIATION: Division of Cardiovascular Diseases and Mandel Center for Hypertension & Atherosclerosis Research, Department of Medicine, GSRB 2, Box 3178, Duke University Medical Center, Durham, North Carolina 27710, USA. arjundeb@med.unc.edu

Country: United States

AGENCY: United States NHLBI

GRANT: R01-HL081744

ACRONYM: HL

MEDLINETA: Stem Cells

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