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

Publication ,  Journal Article
Deb, A; Davis, BH; Guo, J; Ni, A; Huang, J; Zhang, Z; Mu, H; Dzau, VJ
Published in: Stem Cells
January 2008

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.

Duke Scholars

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Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

January 2008

Volume

26

Issue

1

Start / End Page

35 / 44

Location

England

Related Subject Headings

  • Wnt3A Protein
  • Wnt3 Protein
  • Wnt Proteins
  • Transfection
  • Transcription, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Pluripotent Stem Cells
  • Myocytes, Cardiac
  • Mice
  • Membrane Proteins
 

Citation

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Deb, A., Davis, B. H., Guo, J., Ni, A., Huang, J., Zhang, Z., … Dzau, V. J. (2008). SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Stem Cells, 26(1), 35–44. https://doi.org/10.1634/stemcells.2007-0475
Deb, Arjun, Bryce H. Davis, Jian Guo, Aiguo Ni, Jing Huang, Zhiping Zhang, Hui Mu, and Victor J. Dzau. “SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a.Stem Cells 26, no. 1 (January 2008): 35–44. https://doi.org/10.1634/stemcells.2007-0475.
Deb A, Davis BH, Guo J, Ni A, Huang J, Zhang Z, et al. SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Stem Cells. 2008 Jan;26(1):35–44.
Deb, Arjun, et al. “SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a.Stem Cells, vol. 26, no. 1, Jan. 2008, pp. 35–44. Pubmed, doi:10.1634/stemcells.2007-0475.
Deb A, Davis BH, Guo J, Ni A, Huang J, Zhang Z, Mu H, Dzau VJ. SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Stem Cells. 2008 Jan;26(1):35–44.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

January 2008

Volume

26

Issue

1

Start / End Page

35 / 44

Location

England

Related Subject Headings

  • Wnt3A Protein
  • Wnt3 Protein
  • Wnt Proteins
  • Transfection
  • Transcription, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Pluripotent Stem Cells
  • Myocytes, Cardiac
  • Mice
  • Membrane Proteins