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Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
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Arterial pole progenitors interpret opposing FGF/BMP signals to proliferate or differentiate

Mary Redmond Hutson1, Xiaopei Lily Zeng, Andrew J Kim

  • 1Division of Neonatology, Department of Pediatrics, Neonatal-Perinatal Research Institute, Box 103105, Duke University Medical Center, Durham, NC 27710, USA. mhutson@duke.edu

Development (Cambridge, England)
|August 13, 2010
PubMed

Insights

Multipotent stem cells in the developing heart differentiate into cardiovascular cells. FGF and BMP signaling pathways control stem cell proliferation and differentiation into myocardium, smooth muscle, and endothelial cells.

Area of Science:

  • Cardiovascular biology
  • Developmental biology
  • Stem cell research

Background:

  • A specific stem cell population within the heart field is crucial for forming the arterial pole's myocardium and smooth muscle.
  • These stem cells possess the potential to differentiate into multiple cardiovascular cell types.

Purpose of the Study:

  • To investigate the signaling pathways regulating the proliferation and differentiation of these cardiac stem cells.
  • To elucidate the roles of FGF and BMP signaling in cardiovascular cell fate determination.

Main Methods:

  • Clonal and explant culture experiments were employed to study stem cell behavior.
  • Intracellular pathways including Ras/Erk, PLCgamma, and PI3K were analyzed.
  • In vivo studies examined the effects of pathway inhibition on arterial pole development.

Main Results:

  • BMP signaling promoted myocardial differentiation but not proliferation.
  • FGF signaling enhanced proliferation and smooth muscle differentiation while inhibiting myocardial differentiation.
  • Blocking Ras/Erk promoted myocardial differentiation; PLCgamma and PI3K regulated proliferation.
  • Inhibition of these pathways in vivo led to arterial pole defects.

Conclusions:

  • Arterial pole progenitor differentiation requires BMP signaling and downregulation of the FGF/Ras/Erk pathway.
  • The FGF pathway is essential for maintaining the proliferating stem cell pool and subsequent smooth muscle differentiation.

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