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

被引：96

作者：

Aksoy, Irene ^{[1
,2
,3
,4
]}

Giudice, Vincent ^{[1
,2
,3
]}

Delahaye, Edwige ^{[1
,2
,3
]}

Wianny, Florence ^{[1
,2
,3
]}

Aubry, Maxime ^{[1
,2
,3
]}

Mure, Magali ^{[1
,2
,3
]}

Chen, Jiaxuan ^{[4
]}

Jauch, Ralf ^{[4
,5
]}

Bogu, Gireesh K. ^{[4
]}

Nolden, Tobias ^{[6
]}

Himmelbauer, Heinz ^{[6
,7
,8
]}

Xavier Doss, Michael ^{[8
]}

Sachinidis, Agapios ^{[9
]}

Schulz, Herbert ^{[10
]}

Hummel, Oliver ^{[10
]}

Martinelli, Paola ^{[11
]}

Huebner, Norbert ^{[10
]}

Stanton, Lawrence W. ^{[4
]}

Real, Francisco X. ^{[11
,12
]}

Bourillot, Pierre-Yves ^{[1
,2
,3
]}

Savatier, Pierre ^{[1
,2
,3
]}

机构：

[1] INSERM, U846, F-69500 Bron, France

[2] Stem Cell & Brain Res Inst, F-69500 Bron, France

[3] Univ Lyon 1, F-69003 Lyon, France

[4] Genome Inst Singapore, Singapore 138672, Singapore

[5] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Genome Regulat Lab, Guangzhou 510530, Guangdong, Peoples R China

[6] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[7] Ctr Genom Regulat, Barcelona 08003, Spain

[8] Univ Pompeu Fabra, Barcelona 08003, Spain

[9] Inst Neurophysiol, Ctr Physiol & Pathophysiol, D-50931 Cologne, Germany

[10] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[11] Ctr Nacl Invest Oncol, Madrid 28029, Spain

[12] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08002, Spain

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

KRUPPEL-LIKE FACTOR-4; TRANSCRIPTION FACTORS; SELF-RENEWAL; DEFINITIVE ENDODERM; EXPRESSION; GENE; SOX17; ENHANCER; KRUPPEL-LIKE-FACTOR-4; PLURIPOTENCY;

D O I：

10.1038/ncomms4719

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Kruppel-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.

引用

页数：15

共 55 条

[1]

Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm [J].