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Article: Highly cooperative chimeric super-SOX induces naive pluripotency across species
Title | Highly cooperative chimeric super-SOX induces naive pluripotency across species |
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Authors | |
Keywords | bovine developmental potential engineered transcription factor human iPSC mouse naive pluripotency non-human primate Oct4 porcine POU linker reprogramming reset Sox17 Sox2 Sox2/Oct4 heterodimer structure super-SOX tetraploid complementation |
Issue Date | 22-Dec-2023 |
Publisher | Elsevier |
Citation | Cell Stem Cell, 2023 How to Cite? |
Abstract | Our understanding of pluripotency remains limited: iPSC generation has only been established for a few model species, pluripotent stem cell lines exhibit inconsistent developmental potential, and germline transmission has only been demonstrated for mice and rats. By swapping structural elements between Sox2 and Sox17, we built a chimeric super-SOX factor, Sox2-17, that enhanced iPSC generation in five tested species: mouse, human, cynomolgus monkey, cow, and pig. A swap of alanine to valine at the interface between Sox2 and Oct4 delivered a gain of function by stabilizing Sox2/Oct4 dimerization on DNA, enabling generation of high-quality OSKM iPSCs capable of supporting the development of healthy all-iPSC mice. Sox2/Oct4 dimerization emerged as the core driver of naive pluripotency with its levels diminished upon priming. Transient overexpression of the SK cocktail (Sox+Klf4) restored the dimerization and boosted the developmental potential of pluripotent stem cells across species, providing a universal method for naive reset in mammals. |
Persistent Identifier | http://hdl.handle.net/10722/339422 |
ISSN | 2023 Impact Factor: 19.8 2023 SCImago Journal Rankings: 10.253 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | MacCarthy, Caitlin M | - |
dc.contributor.author | Wu, Guangming | - |
dc.contributor.author | Malik, Vikas | - |
dc.contributor.author | Menuchin-Lasowski, Yotam | - |
dc.contributor.author | Velychko, Taras | - |
dc.contributor.author | Keshet, Gal | - |
dc.contributor.author | Fan, Rui | - |
dc.contributor.author | Bedzhov, Ivan | - |
dc.contributor.author | Church, George M | - |
dc.contributor.author | Jauch, Ralf | - |
dc.contributor.author | Cojocaru, Vlad | - |
dc.contributor.author | Schöler, Hans R | - |
dc.contributor.author | Velychko, Sergiy | - |
dc.date.accessioned | 2024-03-11T10:36:29Z | - |
dc.date.available | 2024-03-11T10:36:29Z | - |
dc.date.issued | 2023-12-22 | - |
dc.identifier.citation | Cell Stem Cell, 2023 | - |
dc.identifier.issn | 1934-5909 | - |
dc.identifier.uri | http://hdl.handle.net/10722/339422 | - |
dc.description.abstract | <p>Our understanding of pluripotency remains limited: <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/induced-pluripotent-stem-cell" title="Learn more about iPSC from ScienceDirect's AI-generated Topic Pages">iPSC</a> generation has only been established for a few model species, pluripotent stem cell lines exhibit inconsistent developmental potential, and <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/germline" title="Learn more about germline from ScienceDirect's AI-generated Topic Pages">germline</a> transmission has only been demonstrated for mice and rats. By swapping structural elements between Sox2 and Sox17, we built a chimeric super-SOX factor, Sox2-17, that enhanced iPSC generation in five tested species: mouse, human, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/macaca-fascicularis" title="Learn more about cynomolgus monkey from ScienceDirect's AI-generated Topic Pages">cynomolgus monkey</a>, cow, and pig. A swap of <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/alanine" title="Learn more about alanine from ScienceDirect's AI-generated Topic Pages">alanine</a> to <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/valine" title="Learn more about valine from ScienceDirect's AI-generated Topic Pages">valine</a> at the interface between Sox2 and Oct4 delivered a gain of function by stabilizing Sox2/Oct4 <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/dimerization" title="Learn more about dimerization from ScienceDirect's AI-generated Topic Pages">dimerization</a> on <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/dna" title="Learn more about DNA from ScienceDirect's AI-generated Topic Pages">DNA</a>, enabling generation of high-quality OSKM iPSCs capable of supporting the development of healthy all-iPSC mice. Sox2/Oct4 dimerization emerged as the core driver of naive pluripotency with its levels diminished upon priming. Transient overexpression of the SK cocktail (Sox+Klf4) restored the dimerization and boosted the developmental potential of pluripotent stem cells across species, providing a universal method for naive reset in mammals.</p> | - |
dc.language | eng | - |
dc.publisher | Elsevier | - |
dc.relation.ispartof | Cell Stem Cell | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | bovine | - |
dc.subject | developmental potential | - |
dc.subject | engineered transcription factor | - |
dc.subject | human | - |
dc.subject | iPSC | - |
dc.subject | mouse | - |
dc.subject | naive pluripotency | - |
dc.subject | non-human primate | - |
dc.subject | Oct4 | - |
dc.subject | porcine | - |
dc.subject | POU linker | - |
dc.subject | reprogramming | - |
dc.subject | reset | - |
dc.subject | Sox17 | - |
dc.subject | Sox2 | - |
dc.subject | Sox2/Oct4 heterodimer structure | - |
dc.subject | super-SOX | - |
dc.subject | tetraploid complementation | - |
dc.title | Highly cooperative chimeric super-SOX induces naive pluripotency across species | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.stem.2023.11.010 | - |
dc.identifier.scopus | eid_2-s2.0-85180601019 | - |
dc.identifier.eissn | 1875-9777 | - |
dc.identifier.isi | WOS:001154307800001 | - |
dc.identifier.issnl | 1875-9777 | - |