Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1
Autor: | Yupo Ma, Boon Seng Soh, Bing Lim, Li Chai, Hsiao-Yun Chan, Wai Leong Tam, Paul Robson, Thomas Lufkin, Jianchang Yang, Qiang Wu, Yuefei Lou, Jinqiu Zhang, Huck-Hui Ng, Guo Qing Tong |
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Rok vydání: | 2006 |
Předmět: |
Pluripotent Stem Cells
Chromatin Immunoprecipitation Cell type Transcription Genetic Rex1 Molecular Sequence Data Embryonic Development Electrophoretic Mobility Shift Assay Biology Mice Pregnancy Sequence Homology Nucleic Acid Transcriptional regulation Animals Inner cell mass Promoter Regions Genetic Cell potency Transcription factor Regulation of gene expression Base Sequence Cell Biology Embryo Mammalian Embryonic stem cell Molecular biology eye diseases Cell biology DNA-Binding Proteins Gene Expression Regulation embryonic structures Female Octamer Transcription Factor-3 Transcription Factors |
Zdroj: | Nature Cell Biology. 8:1114-1123 |
ISSN: | 1476-4679 1465-7392 |
Popis: | Embryonic stem (ES) cells are pluripotent cells that can self-renew or differentiate into many cell types. A unique network of transcription factors and signalling molecules are essential for maintaining this capability. Here, we report that a spalt family member, Sall4, is required for the pluripotency of ES cells. Similarly to Oct4, a reduction in Sall4 levels in mouse ES cells results in respecification, under the appropriate culture conditions, of ES cells to the trophoblast lineage. Sall4 regulates transcription of Pou5f1 which encodes Oct4. Sall4 binds to the highly conserved regulatory region of the Pou5f1 distal enhancer and activates Pou5f1 expression in vivo and in vitro. Microinjection of Sall4 small interfering (si) RNA into mouse zygotes resulted in reduction of Sall4 and Oct4 mRNAs in preimplantation embryos and significant expansion of Cdx2 expression into the inner cell mass. These results demonstrate that Sall4 is a transcriptional activator of Pou5f1 and has a critical role in the maintenance of ES cell pluripotency by modulating Oct4 expression. The data also indicates that Sall4 is important for early embryonic cell-fate decisions. |
Databáze: | OpenAIRE |
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