Franziska Meier-Stiegen

Publications (2)6.92 Total impact

• Source

  Available from: Ralf Schwanbeck

  Article: Activated Notch1 target genes during embryonic cell differentiation depend on the cellular context and include lineage determinants and inhibitors.

  Franziska Meier-Stiegen, Ralf Schwanbeck, Kristina Bernoth, Simone Martini, Thomas Hieronymus, David Ruau, Martin Zenke, Ursula Just
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  ABSTRACT: Notch receptor signaling controls developmental cell fates in a cell-context dependent manner. Although Notch signaling directly regulates transcription via the RBP-J/CSL DNA binding protein, little is known about the target genes that are directly activated by Notch in the respective tissues. To analyze how Notch signaling mediates its context dependent function(s), we utilized a Tamoxifen-inducible system to activate Notch1 in murine embryonic stem cells at different stages of mesodermal differentiation and performed global transcriptional analyses. We find that the majority of genes regulated by Notch1 are unique for the cell type and vary widely dependent on other signals. We further show that Notch1 signaling regulates expression of genes playing key roles in cell differentiation, cell cycle control and apoptosis in a context dependent manner. In addition to the known Notch1 targets of the Hes and Hey families of transcriptional repressors, Notch1 activates the expression of regulatory transcription factors such as Sox9, Pax6, Runx1, Myf5 and Id proteins that are critically involved in lineage decisions in the absence of protein synthesis. We suggest that Notch signaling determines lineage decisions and expansion of stem cells by directly activating both key lineage specific transcription factors and their repressors (Id and Hes/Hey proteins) and propose a model by which Notch signaling regulates cell fate commitment and self renewal in dependence of the intrinsic and extrinsic cellular context.
  PLoS ONE 01/2010; 5(7):e11481. · 4.09 Impact Factor
• Article: Activated Notch1 alters differentiation of embryonic stem cells into mesodermal cell lineages at multiple stages of development.

  Timm Schroeder, Franziska Meier-Stiegen, Ralf Schwanbeck, Hanna Eilken, Satomi Nishikawa, Robert Häsler, Stefan Schreiber, Georg W Bornkamm, Shin-Ichi Nishikawa, Ursula Just
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  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.
  Mechanisms of Development 08/2006; 123(7):570-9. · 2.83 Impact Factor