Nature Cell Biology
- 8, 1114 - 1123 (2006)
Published online: 17 September 2006; | doi:10.1038/ncb1481
Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1Jinqiu Zhang1, 8, Wai-Leong Tam1, 2, 8, Guo Qing Tong1, 8, Qiang Wu3, Hsiao-Yun Chan1, Boon-Seng Soh1, Yuefei Lou1, Jianchang Yang4, Yupo Ma4, Li Chai5, Huck-Hui Ng3, 6, Thomas Lufkin1, 6, Paul Robson1, 6 & Bing Lim1, 71
Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672. 2
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456. 3
Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672. 4
Division of Laboratory Medicine, Nevada Cancer Institute, Las Vegas, NV 89135, USA. 5
The Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. 6
Department of Biological Sciences, National University of Singapore, Singapore 117543. 7
Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA. 8
These authors contributed equally to this work.
Correspondence should be addressed to Bing Lim limb1@gis.a-star.edu.sg 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.
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