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Article: Highly cooperative chimeric super-SOX induces naive pluripotency across species

TitleHighly cooperative chimeric super-SOX induces naive pluripotency across species
Authors
MacCarthy, Caitlin MWu, GuangmingMalik, VikasMenuchin-Lasowski, YotamVelychko, TarasKeshet, GalFan, RuiBedzhov, IvanChurch, George MJauch, RalfCojocaru, VladSchöler, Hans RVelychko, Sergiy
Keywordsbovine
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 Date22-Dec-2023
PublisherElsevier
Citation
Cell Stem Cell, 2023 How to Cite?
DOI: http://dx.doi.org/10.1016/j.stem.2023.11.010
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 Identifierhttp://hdl.handle.net/10722/339422
ISSN
1934-5909
2023 Impact Factor: 19.8
2023 SCImago Journal Rankings: 10.253
ISI Accession Number ID
WOS:001154307800001

 

DC FieldValueLanguage
dc.contributor.authorMacCarthy, Caitlin M-
dc.contributor.authorWu, Guangming-
dc.contributor.authorMalik, Vikas-
dc.contributor.authorMenuchin-Lasowski, Yotam-
dc.contributor.authorVelychko, Taras-
dc.contributor.authorKeshet, Gal-
dc.contributor.authorFan, Rui-
dc.contributor.authorBedzhov, Ivan-
dc.contributor.authorChurch, George M-
dc.contributor.authorJauch, Ralf-
dc.contributor.authorCojocaru, Vlad-
dc.contributor.authorSchöler, Hans R-
dc.contributor.authorVelychko, Sergiy -
dc.date.accessioned2024-03-11T10:36:29Z-
dc.date.available2024-03-11T10:36:29Z-
dc.date.issued2023-12-22-
dc.identifier.citationCell Stem Cell, 2023-
dc.identifier.issn1934-5909-
dc.identifier.urihttp://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.languageeng-
dc.publisherElsevier-
dc.relation.ispartofCell Stem Cell-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectbovine-
dc.subjectdevelopmental potential-
dc.subjectengineered transcription factor-
dc.subjecthuman-
dc.subjectiPSC-
dc.subjectmouse-
dc.subjectnaive pluripotency-
dc.subjectnon-human primate-
dc.subjectOct4-
dc.subjectporcine-
dc.subjectPOU linker-
dc.subjectreprogramming-
dc.subjectreset-
dc.subjectSox17-
dc.subjectSox2-
dc.subjectSox2/Oct4 heterodimer structure-
dc.subjectsuper-SOX-
dc.subjecttetraploid complementation-
dc.titleHighly cooperative chimeric super-SOX induces naive pluripotency across species-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.stem.2023.11.010-
dc.identifier.scopuseid_2-s2.0-85180601019-
dc.identifier.eissn1875-9777-
dc.identifier.isiWOS:001154307800001-
dc.identifier.issnl1875-9777-

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