|
| Status |
Public on Sep 13, 2018 |
| Title |
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Self-renewal of embryonic stem cells (ESCs) cultured in serum-LIF is incomplete with some cells initiating differentiation. While this is reflected in heterogeneous expression of naive pluripotency transcription factors (TFs), the link between TF heterogeneity and differentiation is not fully understood. Here we purify ESCs with distinct TF expression levels from serum-LIF cultures to uncover early events during commitment from naïve pluripotency. ESCs carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in NANOGlow cells. Independent Esrrb reporter lines demonstrate that ESRRBnegative ESCs cannot effectively self-renew. Upon ESRRB loss, pre-implantation pluripotency gene expression collapses. ChIP-Seq identifies different regulatory element classes that bind both OCT4 and NANOG in ESRRBhigh cells. Class I elements lose NANOG and OCT4 binding in ESRRBnegative ESCs and associate with genes expressed preferentially in naïve ESCs. In contrast, class II elements retain OCT4 but not NANOG binding in ESRRBnegative cells and associate with more broadly expressed genes. Therefore, mechanistic differences in TF function act cumulatively to restrict potency during exit from naïve pluripotency.
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| |
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| Overall design |
ChIP-seq for Oct4 and Nanog in ESCs sorted by Esrrb level (high, medium, negative), 6 datasets total
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| |
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| Contributor(s) |
Festuccia N, Halbritter F, Corsinotti A, Gagliardi A, Colby D, Tomlinson SR, Chambers I |
| Citation(s) |
30275266 |
| |
| Submission date |
Aug 22, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Florian Halbritter |
| Organization name |
St. Anna Children's Cancer Research Institute (CCRI)
|
| Lab |
Developmental Cancer Genomics
|
| Street address |
Zimmermannplatz 10
|
| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE118907 |
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation. |
|
| Relations |
| BioProject |
PRJNA487261 |
| SRA |
SRP158598 |
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