SPREDs (Sprouty related proteins with EVH1 domain) promote self-renewal and inhibit mesodermal differentiation in murine embryonic stem cells
| Autor: | Bastian, Mühl, Jasmin, Hägele, Alpaslan, Tasdogan, Paraskevi, Loula, Kai, Schuh, Karin, Bundschu |
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| Rok vydání: | 2014 |
| Předmět: |
STAT3 Transcription Factor
MAP Kinase Signaling System Apoptosis Cell Differentiation Mice Transgenic Leukemia Inhibitory Factor Mesoderm Repressor Proteins Mice Phosphatidylinositol 3-Kinases Image Processing Computer-Assisted Animals Humans Female Extracellular Signal-Regulated MAP Kinases Embryonic Stem Cells Adaptor Proteins Signal Transducing Cell Proliferation Signal Transduction |
| Zdroj: | Developmental dynamics : an official publication of the American Association of Anatomists. 244(4) |
| ISSN: | 1097-0177 |
| Popis: | Pluripotency, self-renewal, and differentiation are special features of embryonic stem (ES) cells, thereby providing valuable perspectives in regenerative medicine. Developmental processes require a fine-tuned organization, mainly regulated by the well-known JAK/STAT, PI3K/AKT, and ERK/MAPK pathways. SPREDs (Sprouty related proteins with EVH1 domain) were discovered as inhibitors of the ERK/MAPK signaling pathway, whereas nothing was known about their functions in ES cells and during early differentiation, so far.We generated SPRED1 and SPRED2 overexpressing and SPRED2 knockout murine ES cells to analyze the functions of SPRED proteins in ES cells and during early differentiation. Overexpression of SPREDs increases significantly the self-renewal and clonogenicity of murine ES cells, whereas lack of SPRED2 reduces proliferation and increases apoptosis. During early differentiation in embryoid bodies, SPREDs promote the pluripotent state and inhibit differentiation whereby mesodermal differentiation into cardiomyocytes is considerably delayed and inhibited. LIF- and growth factor-stimulation revealed that SPREDs inhibit ERK/MAPK activation in murine ES cells. However, no effects were detectable on LIF-induced activation of the JAK/STAT3, or PI3K/AKT signaling pathway by SPRED proteins.We show that SPREDs promote self-renewal and inhibit mesodermal differentiation of murine ES cells by selective suppression of the ERK/MAPK signaling pathway in pluripotent cells. |
| Databáze: | OpenAIRE |
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