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Updated: May 10, 2026

Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo
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Published on: February 2, 2016

Shox2 regulates the pacemaker gene program in embryoid bodies.

Sherin I Hashem1, May L Lam, Shirley S Mihardja

  • 11 Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center , New Orleans, Louisiana.

Stem Cells and Development
|June 18, 2013
PubMed
Summary

Researchers developed an in vitro model using mouse embryonic stem cells to study heart pacemaker development. Ablating Shox2 disrupted pacemaker function, a phenotype rescued by BMP4, offering insights into cardiac arrhythmias.

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Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
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Published on: February 17, 2015

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Last Updated: May 10, 2026

Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo
11:13

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Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
08:52

Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection

Published on: February 17, 2015

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Stem Cell Research

Background:

  • The heart's rhythmic beating originates from specialized pacemaker tissues, primarily the sinoatrial node (SAN).
  • Understanding the genetic regulation of pacemaker development is vital for treating cardiac arrhythmias.
  • Existing models lack the complexity to fully recapitulate in vivo cardiac tissue formation.

Purpose of the Study:

  • To establish a reproducible in vitro model for studying cardiac pacemaker and contracting tissue development.
  • To investigate the role of the Shox2 gene in the formation and function of cardiac pacemaker tissues.
  • To identify key molecular pathways, including BMP4 signaling, involved in pacemaker development.

Main Methods:

  • Utilized three-dimensional aggregate cultures of mouse embryonic stem cells (embryoid bodies, EBs).
  • Employed genetic marker expression and electrophysiological analyses to assess tissue formation and function.
  • Investigated the effects of Shox2 ablation and BMP4 manipulation (using Noggin) on EB development.

Main Results:

  • Demonstrated self-organized formation of pacemaker and contracting tissues within EBs, creating a functional syncytium.
  • Shox2 ablation led to slowed contraction rates and altered expression of key cardiac development genes (HCN4, Cx45, Tbx2, Tbx3, BMP4, Cx40, Cx43, Nkx2.5, Tbx5).
  • BMP4 supplementation rescued the Shox2 knockout phenotype, and BMP4 inhibition mimicked the knockout phenotype.

Conclusions:

  • Successfully generated a novel in vitro model (EBs) for studying cardiac pacemaker development.
  • Confirmed Shox2 as a critical determinant in the SAN genetic pathway and highlighted the importance of BMP4 signaling.
  • The model provides a valuable platform for future research into cardiac development and arrhythmia mechanisms.