MTZ®-MPI-Award 2020 to Dr. Sergiy Velychko

On 27th November 2020, the MTZ®foundation honors Dr. Sergiy Velychko. He has published significant work in the department of Professor Dr. Hans Schöler at the Max Planck Institute for Molecular Biomedicine on mechanisms that lead to a dramatic improvement in the quality of induced pluripotent stem cells by eliminating the factor that was previously considered crucial.
Since 2009, the MTZ®foundation annually honors young scientists at the MPI for Molecular Biomedicine with the MTZ®-MPI Award, which is endowed with 2,500 euros. In this way, the donor couple Monika and Thomas Zimmermann would like to support young people on their way into research.

Less is more – how the quality of induced pluripotent stem cells is dramatically enhanced by omitting what was thought to be the most crucial reprogramming factor

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, who did his PhD in the department of 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 iPSCs were created", says Velychko.

If this works the same way in human cells, it has great implications for potential clinical applications of iPSCs.

About Sergiy Velychko

Sergiy Velychko (31) 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 successfully defended his thesis in November 2020. Velychko's main scientific interests include stem cells, development and reprogramming of cell fate.

Sergiy Velychko has eight publications as a PhD student, two very good ones as first author in Cell Stem Cell and Cell Reports. Two more first author publications are in the pipeline. The Cell Stem Cell publication "Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs" is considered a key paper in the stem cell field and was the most downloaded publication of Cell Stem Cell for weeks. It is in a special issue of the Top 10 Cell Stem Cell Publications 2019 and was also voted Paper of the Year by the German Stem Cell Network.

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