Related Experiment Video
Updated: Aug 7, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
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
Abstract:
Signals of Notch transmembrane receptors function to regulate a wide variety of developmental cell fates. Here we investigate the role of Notch signaling in the development of mesodermal cell types by expressing a tamoxifen-inducible, activated form of Notch1 in embryonic stem cells (ESC). For differentiation of ESC into first mesodermal progenitor cells and then endothelial, mural, cardiac muscle and hematopoietic cells, the OP9 stroma co-culture system was used. Timed activation of Notch signaling by the addition of tamoxifen at various stages during differentiation of ESC into mesodermal cell lineages results in profound alterations in the generation of all of these cells. Differentiation of ESC into Flk1(+) mesodermal cells is inhibited by activated Notch. When Notch signaling is activated in mesodermal cells, generation of cardiac muscle, endothelial and hematopoietic cells is inhibited, favoring the generation of mural cells. Activation of Notch signaling in hematopoietic cells reduces colony formation and maintenance of hematopoiesis. These data suggest that Notch signaling plays a regulatory role in mesodermal development, cardiomyogenesis, the balanced generation of endothelial versus mural cells of blood vessels and hematopoietic development.
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.
Related Concept Videos
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Stem Cell Niche
Maintenance of the ES Cell State
Determination
Gastrulation
Lineage Commitment

