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Status |
Public on Feb 10, 2024 |
Title |
Removing an acid residue is necessary and sufficient to turn SOX17 into a pluripotency factor |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
SOX17 directs the differentiation of the extraembryonic endoderm and acts as a human germline specifier. The replacement of an acidic residue at position 57 with a basic residue found in SOX2 turns SOX17 into a pluripotency factor. Here we systematically interrogated how mutations at this critical position affect the cellular reprogramming activity of SOX17. We found that most mutations turn SOX17 into a pluripotency factor regardless of their biophysical properties. The mutation to an aspartate allows the SOX17E57D protein to maintain a self-renewing endodermal state. Only the glutamate found in the wild-type protein can effectively block a SOX17/OCT4 dimer from binding composite DNA elements found in pluripotency enhancers. Insights into how modifications of an ultra-conserved residue affect functions of developmental transcription factor provide avenues to advance cell fate engineering.
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Overall design |
To investigate the effects SOX17E57 variants have on maintaining pluripotency, SOX2 or the SOX17E57 variants were introduced into engineered Tet-Off Sox2 mESCs (also known as the 2TS22C cell line) using lentiviruses. Cells were cultured in mouse serum/LIF/2i medium for ten passages prior to analysis.
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Contributor(s) |
Ho S, Jauch R |
Citation missing |
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Submission date |
Feb 05, 2024 |
Last update date |
Feb 10, 2024 |
Contact name |
Sik Yin Ho |
E-mail(s) |
jessiehsy3590@gmail.com
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Organization name |
The University of Hong Kong
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Street address |
Laboratory Block, 21 Sassoon Block
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City |
Hong Kong |
ZIP/Postal code |
00000 |
Country |
Hong Kong |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (8)
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Relations |
BioProject |
PRJNA1073433 |