🙏 A. Wenzel, K. Uściło, S. Kompocholi, S. Bages-Arnal,
@gemnov.bsky.social

Using HDAC3 knockout embryos, we show that they typically fail to implant, and if they manage, they are very small and upregulate the most active genes. It is fascinating how a repressor of enhancers regulates the most active genes, allowing for development and to proceed.

At enhancers HDAC3 fights with P300, an activator, to reduce the expression of the most active fraction of the genome. Losing HDAC3 boosts the levels of pluripotency and prevents them from efficiently differentiating.

We found that HDAC3, a histone deacetylase, is an intriguing transcriptional repressor. Rather than maintaining genes in a silent state, it is recruited to the most active enhancers of mouse pluripotent stem cells.

Wow huge congratulations!

We also find that there is robust reductive glutamine metabolism in stem cells with glutamine becoming the most prominent source of carbon for histone acetylation

Pyruvate emerged as a vital metabolic nexus in pluripotent stem cells, with high pyruvate carboxylase and malic enzyme activity. Functionally, this is crucial for the timely exit from naive pluripotency and maintaining histone acetylation levels.

We used 13C labeling and imaging MS to uncover how metabolism rewires when the mouse embryo implants. We found that there is no simple TCA cycle shutdown; rather, there is intricate rewiring. This process is recapitulated in pluripotent stem cells cultured under low oxygen.

This was a great collaboration lead by Karlien Van Nerum with @sophiepetropoulos.bsky.social ThomasMoritz and EpiQMax.

The grass is always greener on the other side. But for now Denmark is a pretty nice place to live and do research! We mainly complain about the weather.

Congratulations!!! This is great news!!