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Highly regarded study on iPSC reprogramming shows that Oct4 is not only unnecessary, but actually reduces the developmental potential of iPSCs
Every year, the German Stem Cell Network honours the best best publication of German origin in the field of stem cell research. The “GSCN 2020 Publication of the Year Award” goes to Sergiy Velychko, PhD student at the Max Planck Institute for Molecular Biomedicine, and his mentor Hans Schöler. In November 2019, they published an internationally acclaimed study in Cell Stem Cell. The award is endowed with 1,500 Euro. Velychko is invited to give a lecture at the Presidential Symposium on September 24, 2020. The event, and thus the presentation of the award, will take place this year as an online event.
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The iPSC technology pioneered by Shinya Yamanaka allows for reprogramming of adult cells, such as skin fibroblasts, back to an embryonic stem cell (ESC)-like state. Because the forced overexpression of four transcription factors induces the all-round differentiation ability (called pluripotency) in somatic cells, the resulting cells are called induced pluripotent stem cells (iPSCs).
While posited by many as the ultimate replacement of ESCs, multiple studies showed that iPSCs do not quite match the ‘gold standard’ ESCs in their developmental potential. The reprogramming process, i.e. the way in which the introduced factors reverse the epigenetic landscape of mature cells, often trigger errors, which means that many iPSC lines reprogrammed with Yamanaka factors are unable to support normal differentiation. The exact origin of or agent that causes these changes has never been determined.
Sergiy Velychko, a PhD student with Hans Schöler, wanted to investigate the roles of the different components of the Yamanaka cocktail (Oct4, Sox2, Klf4 and cMyc - OSKM) in reprogramming to pluripotency. To do this, he created reprogramming vectors with different combinations of the Yamanaka factors.
The young researcher was surprised by the results: "Not only could the vector without Oct4, which was actually supposed to serve as a negative control, produce iPSCs.”
Other studies that used an SKM construct did not show any reprogramming. "We later found that the discrepancy to earlier studies could be explained by the retroviral vectors used by Yamanaka and many others in their experiments," Velychko says. "These retroviral vectors can silence themselves, thereby ending the reprogramming process in an early stage."
The fact that reprogramming without Oct4 produced fewer colonies with some delay is secondary. Because: "Compared to conventional OSKM iPSCs, better quality iPSC were created", says Velychko.
“If this works the same way in human cells, it has great implications for potential clinical applications of iPSCs,” says Hans Schöler.
Sergiy Velychko's study in Cell Stem Cell (November 7, 2019) attracted worldwide attention: 'The Scientist', a New York City-based journal for life scientists named the study “Top Technical Advances of 2019”, and 'The Stem Cell Podcast' reported on his work. Lastly, the journal Cell Stem Cell selected the study in the Top 10 most read articles in 2019.
About Sergiy Velychko
Sergiy Velychko received his BSc in Biology at the National University of Kyiv (Ukraine), and his MSc in Molecular Bioengineering at the Technical University of Dresden. Sergiy Velychko started his PhD work in the lab of professor Hans R. Schöler at the Max Planck Institute for Molecular Biomedicine in October 2012 and will finish within two months. Velychko’s main scientific interests include stem cells, development, and reprogramming cell fate. He co-authored 7 articles and he has two first-author publications.
About Hans Schöler
You will find Hans Schöler's CV here: https://www.mpi-muenster.mpg.de/97800/cv
About the German Stem Cell Network
The GSCN was founded in 2013 and aims to better network, support and disseminate its results and research to a broad public. The promotion of young scientists and the presentation of outstanding women scientists are of particular importance to the GSCN.
Since 2015, the GSCN annually presents three awards: the GSCN Young Investigator Award, the GSCN Female Investigator Award and the GSCN Publication of the Year. The three GSCN Awards are endowed with 1,500 Euros each and the awardees give a 30 minute-lecture at the Presidential Symposium of the annual conference. This year's Annual GSCN Conference from 23 to 25 September 2020 will take place as an online event.
https://www.mpi-muenster.mpg.de/576398/20200827-gscn-publication-of-the-year
Sergiy Velychko
Sergiy Velychko
Hans Schöler
Max Planck Institute for Molecular Biomedicine / J. Müller-Keuker
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