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| Status |
Public on Sep 23, 2019 |
| Title |
Endogenous fluctuations of OCT4 and SOX2 bias pluripotent cell fate decisions |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
SOX2 and OCT4 are pioneer transcription factors playing a key role in embryonic stem (ES) cell self-renewal and differentiation. How temporal fluctuations in their expression levels bias lineage commitment is unknown. Here we generated knock-in reporter fusion ES cell lines allowing to monitor endogenous SOX2 and OCT4 protein fluctuations in living cells and to determine their impact on mesendodermal and neuroectodermal commitment. We found that small differences in SOX2 and OCT4 levels impact cell fate commitment in G1 but not in S phase. Elevated SOX2 levels modestly increased neuroectodermal commitment and decreased mesendodermal commitment upon directed differentiation. In contrast, elevated OCT4 levels strongly biased ES cells towards both neuroectodermal and mesendodermal fates. Using ATAC-seq on ES cells gated for different endogenous SOX2 and OCT4 levels, we found that high OCT4 levels increased chromatin accessibility at differentiation-associated enhancers. This suggests that small endogenous fluctuations of pioneer transcription factors can bias cell fate decisions by concentration-dependent priming of differentiation-associated enhancers.
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| Overall design |
Cells were subjected to ATAC-seq by Tn5 transposition or to ChIP-seq by immunoprecipitation
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| Contributor(s) |
Suter DM, Friman ET |
| Citation(s) |
31556488 |
| |
| Submission date |
Feb 14, 2019 |
| Last update date |
Oct 08, 2019 |
| Contact name |
David Michael Suter |
| Organization name |
École polytechnique fédérale de Lausanne
|
| Department |
Institute of Bioengineering
|
| Lab |
UPSUTER
|
| Street address |
EPFL SV-IN Station 19
|
| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA522359 |
| SRA |
SRP185880 |
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