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Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells

Item Type:Article
Title:Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
Creators Name:Aksoy, I. and Giudice, V. and Delahaye, E. and Wianny, F. and Aubry, M. and Mure, M. and Chen, J. and Jauch, R. and Bogu, G.K. and Nolden, T. and Himmelbauer, H. and Doss, M.X. and Sachinidis, A. and Schulz, H. and Hummel, O. and Martinelli, P. and Huebner, N. and Stanton, L.W. and Real, F.X. and Bourillot, P.Y. and Savatier, P.
Abstract:Krueppel-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.
Keywords:Cell Differentiation, Chromatin Immunoprecipitation, Developmental Gene Expression Regulation, Embryonic Stem Cells, Endoderm, Flow Cytometry, Gene Knockdown Techniques, High-Throughput Nucleotide Sequencing, Kruppel-Like Transcription Factors, Mesoderm, Microarray Analysis, Real-Time Polymerase Chain Reaction, Western Blotting, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:5
Page Range:3719
Date:28 April 2014
Official Publication:https://doi.org/10.1038/ncomms4719
PubMed:View item in PubMed

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