Activated Notch1 alters differentiation of embryonic stem cells into mesodermal cell lineages at multiple stages of

Timm Schroeder1, Franziska Meier-Stiegen, Ralf Schwanbeck

  • 1Institute for Clinical Molecular Biology and Tumor Genetics, GSF - National Research Center for Environment and Health, Marchioninistr. 25, 81377 München, Germany. timm.schroeder@gsf.de

Insights

Notch signaling regulates embryonic development. Activating Notch1 in stem cells alters mesodermal cell generation, impacting cardiac, blood vessel, and hematopoietic cell development.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Stem Cell Biology

Background:

  • Notch transmembrane receptors are crucial for regulating diverse developmental cell fates.
  • Understanding Notch signaling's role in mesodermal lineage development is essential for regenerative medicine and developmental studies.

Purpose of the Study:

  • To investigate the role of Notch signaling in the development of mesodermal cell types.
  • To determine how timed activation of Notch1 signaling affects differentiation of embryonic stem cells (ESC) into various mesodermal lineages.

Main Methods:

  • Utilized a tamoxifen-inducible, activated form of Notch1 expressed in ESC.
  • Employed the OP9 stroma co-culture system for differentiation into mesodermal progenitor, endothelial, mural, cardiac muscle, and hematopoietic cells.
  • Administered tamoxifen at various differentiation stages to control Notch activation timing.

Main Results:

  • Activated Notch signaling inhibited differentiation of ESC into Flk1(+) mesodermal cells.
  • Activation in mesodermal cells suppressed cardiac muscle, endothelial, and hematopoietic cell generation, promoting mural cell production.
  • Notch activation in hematopoietic cells reduced colony formation and hematopoietic maintenance.

Conclusions:

  • Notch signaling plays a critical regulatory role in mesodermal development.
  • It influences cardiomyogenesis and the balance between endothelial and mural cell generation in blood vessels.
  • Notch signaling is important for proper hematopoietic development.

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