TY - JOUR
T1 - Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells
AU - Aksoy, Irène
AU - Giudice, Vincent
AU - Delahaye, Edwige
AU - Wianny, Florence
AU - Aubry, Maxime
AU - Mure, Magali
AU - Chen, Jiaxuan
AU - Jauch, Ralf
AU - Bogu, Gireesh K.
AU - Nolden, Tobias
AU - Himmelbauer, Heinz
AU - Doss, Michael Xavier
AU - Sachinidis, Agapios
AU - Schulz, Herbert
AU - Hummel, Oliver
AU - Martinelli, Paola
AU - Hübner, Norbert
AU - Stanton, Lawrence W.
AU - Real, Francisco X.
AU - Bourillot, Pierre Yves
AU - Savatier, Pierre
PY - 2014/4/28
Y1 - 2014/4/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899653339&partnerID=8YFLogxK
U2 - 10.1038/ncomms4719
DO - 10.1038/ncomms4719
M3 - Article
C2 - 24770696
AN - SCOPUS:84899653339
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 3719
ER -