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| Status |
Public on Jan 11, 2016 |
| Title |
NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Nanog, a core pluripotency factor in the inner cell mass of blastocysts, is also expressed in unipotent primordial germ cells (PGC) in mice1, where its precise role is yet unclear2-4. We investigated this in an in vitro model, where naïve pluripotent embryonic stem cells (ESCs) cultured in bFGF/ActivinA develop as epiblast-like cells (EpiLCs), and gain competence for PGC-like fate5. Consequently, bone morphogenetic protein (BMP4), or ectopic expression of key germline transcription factors Prdm1/ Prdm14/ Tfap2c, directly induce PGC-like cells (PGCLCs) in EpiLCs, but not in ESCs6-8. Here we report an unexpected discovery that Nanog alone can induce PGCLCs in EpiLCs, independently of BMP4. We propose that following the dissolution of the naïve ESC pluripotency network during establishment of EpiLCs9,10, the epigenome is reset for cell fate determination. Indeed, we found genome-wide changes in NANOG binding pattern between ESCs and EpiLCs, indicating epigenetic resetting of regulatory elements. Accordingly, we show that NANOG can bind and activate enhancers of Prdm1 and Prdm14 in EpiLCs in vitro; BLIMP1 (encoded by Prdm1) then directly induces Tfap2c. Furthermore, while SOX2 and NANOG promote the pluripotent state in ESCs, they show contrasting roles in EpiLCs since Sox2 specifically represses PGCLC induction by Nanog. This study demonstrates a broadly applicable mechanistic principle for how cells acquire competence for cell fate determination, resulting in the context-dependent roles of key transcription factors during development.
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| Overall design |
Refer to individual Series
|
| |
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| Citation(s) |
26751055 |
| |
| Submission date |
Aug 11, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Sabine Dietmann |
| Organization name |
Washington University School of Medicine
|
| Street address |
4565 McKinley Avenue
|
| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (18)
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| This SuperSeries is composed of the following SubSeries: |
| GSE61924 |
NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers [microarray] |
| GSE71932 |
NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers [ChIP-seq] |
|
| Relations |
| BioProject |
PRJNA292497 |
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