Your browser doesn't support javascript.
loading
Highly cooperative chimeric super-SOX induces naive pluripotency across species.
MacCarthy, Caitlin M; Wu, Guangming; Malik, Vikas; Menuchin-Lasowski, Yotam; Velychko, Taras; Keshet, Gal; Fan, Rui; Bedzhov, Ivan; Church, George M; Jauch, Ralf; Cojocaru, Vlad; Schöler, Hans R; Velychko, Sergiy.
Affiliation
  • MacCarthy CM; Max Planck Institute for Molecular Biomedicine, Münster, Germany.
  • Wu G; Max Planck Institute for Molecular Biomedicine, Münster, Germany; International Bio Island, Guangzhou, China; MingCeler Biotech, Guangzhou, China.
  • Malik V; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
  • Menuchin-Lasowski Y; Max Planck Institute for Molecular Biomedicine, Münster, Germany.
  • Velychko T; Max Planck Institute for Molecular Biomedicine, Münster, Germany; Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
  • Keshet G; Hebrew University of Jerusalem, Jerusalem, Israel.
  • Fan R; Max Planck Institute for Molecular Biomedicine, Münster, Germany.
  • Bedzhov I; Max Planck Institute for Molecular Biomedicine, Münster, Germany.
  • Church GM; Department of Genetics, Harvard Medical School, Boston, MA, USA; Wyss Institute, Harvard University, Boston, MA, USA.
  • Jauch R; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Centre for Translational Stem Cell Biology, Hong Kong SAR, China.
  • Cojocaru V; Max Planck Institute for Molecular Biomedicine, Münster, Germany; University of Utrecht, Utrecht, the Netherlands; STAR-UBB Institute, Babes-Bolyai University, Cluj-Napoca, Romania.
  • Schöler HR; Max Planck Institute for Molecular Biomedicine, Münster, Germany. Electronic address: h.schoeler@mpi-muenster.mpg.de.
  • Velychko S; Max Planck Institute for Molecular Biomedicine, Münster, Germany; Department of Genetics, Harvard Medical School, Boston, MA, USA; Wyss Institute, Harvard University, Boston, MA, USA. Electronic address: sergiy_velychko@hms.harvard.edu.
Cell Stem Cell ; 31(1): 127-147.e9, 2024 01 04.
Article in En | MEDLINE | ID: mdl-38141611
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.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pluripotent Stem Cells / Induced Pluripotent Stem Cells Limits: Animals / Humans Language: En Journal: Cell Stem Cell Year: 2024 Document type: Article Affiliation country:
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pluripotent Stem Cells / Induced Pluripotent Stem Cells Limits: Animals / Humans Language: En Journal: Cell Stem Cell Year: 2024 Document type: Article Affiliation country: