Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
| Autor: | Pierre-Yves Bourillot, Pierre Savatier, Herbert Schulz, Magali Mure, Gireesh K. Bogu, Florence Wianny, Jiaxuan Chen, Agapios Sachinidis, Maxime Aubry, Oliver Hummel, Paola Martinelli, Lawrence W. Stanton, Tobias Nolden, Edwige Delahaye, Vincent Giudice, Norbert Hubner, Heinz Himmelbauer, Ralf Jauch, Francisco X. Real, Michael Xavier Doss, Irene Aksoy |
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| Rok vydání: | 2014 |
| Předmět: |
Chromatin Immunoprecipitation
Mesoderm animal structures Cellular differentiation Blotting Western Kruppel-Like Transcription Factors General Physics and Astronomy Biology Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Kruppel-Like Factor 4 Mice medicine Animals Induced pluripotent stem cell Embryonic Stem Cells Genetics Multidisciplinary Endoderm Gene Expression Regulation Developmental High-Throughput Nucleotide Sequencing Cell Differentiation General Chemistry Flow Cytometry Microarray Analysis Embryonic stem cell Cell biology medicine.anatomical_structure KLF4 Gene Knockdown Techniques embryonic structures NODAL Definitive endoderm |
| Zdroj: | Nature Communications. 5 |
| ISSN: | 2041-1723 |
| Popis: | Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells. |
| Databáze: | OpenAIRE |
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