Jan Żylicz

🧵1/14 Preprint thread! Can we predict a cell’s fate based on its dynamics? 🔮 Our new study unveils a framework for watching development unfold in real-time, revealing how a cell's shape and movement encode info about its future fate. 🔬📄 Preprint: tinyurl.com/4shf8v4x

🙏 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.

HDAC3 prevents enhancer hyperactivation to enable developmental transitions Dynamic gene regulation requires precise cooperation between transcription factors and chromatin modifiers at regulatory elements to achieve not only activation or repression, but also appropriate tra...

Genes are not On/Off switches. In a new preprint we show that HDAC3 is key to establish correct transcriptional dose in development. Gr8 work from N. Stamidis @ucph.bsky.social and collab. @jamiehackett.bsky.social @gregersenlab.bsky.social . Huge thx to all authors! www.biorxiv.org/content/10.1...

It’s always a bit awkward to write about personal experiences. I tried to touch on what Pride means to me and ended up reflecting on heteronormativity, passing, and allyship. Thank you @slefkopoulos.bsky.social for the great opportunity! @ucph.bsky.social
#LGBTQIA+ #PRIDE #Diversity

There is still some time to secure your spot at the next Niche meeting in CPH. We have a great lineup of speakers! @novo-nordisk.bsky.social sciencecluster.dk/event/confer...

I could not have been more proud! The first student from the lab just defended his PhD in great style!! Congratulations Arnau Casòliba Melich !!! A huge thank you to the committee @bernasozen.bsky.social Ana Boskovic and @aramariaceleste.bsky.social

Wow huge congratulations!

It was fun to chat with @amjeve.bsky.social about my fantastic mentors and how it is to become independent at reNEW_Global @ucph.bsky.social

α-Ketoglutarate promotes trophectoderm induction and maturation from naive human embryonic stem cells - Nature Cell Biology Van Nerum et al. show that dimethyl α-ketoglutarate enhances the production and functional maturation of human trophectoderm-like cells from embryonic stem cells by regulating histone acetyltransferas...

💫NEW: @jzylicz.bsky.social & co show that dimethyl α-ketoglutarate enhances the production and functional maturation of human #trophectoderm - like cells from embryonic #StemCells by regulating histone acetyltransferase activity and the pluripotency network.
bit.ly/3EGflmL

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.

TCA cycle rewiring underpins implantation and histone acetylation programming Metabolism has emerged as a key regulator of stem cell differentiation and their epigenomes. This coupling is particularly evident during the exit from naive pluripotency in vitro. However, our unders...

In a new preprint with @trabelink.bsky.social, T. Moritz & @bonalditiziana.bsky.social, we find that implantation leads to rewiring of the TCA cycle to support histone acetylation turnover and exit from naïve pluripotency. Gr8 work of @elenikafkia.bsky.social D. Pladevall-Morera et al. rb.gy/clk8vm

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

α-Ketoglutarate promotes trophectoderm induction and maturation from naive human embryonic stem cells - Nature Cell Biology Van Nerum et al. show that dimethyl α-ketoglutarate enhances the production and functional maturation of human trophectoderm-like cells from embryonic stem cells by regulating histone acetyltransferas...

Can metabolism regulate more than bioenergetics during human development? Our new study says YES! We show that metabolism influences cell fate choice in human naïve pluripotent stem cells, histone acetylation, and trophectoderm maturation. rb.gy/spqr9j
@natcellbio.nature.com

Junior Group Leader (Associate Professor) in Stem Cell Medicine Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW Department of Biomedical Sciences Faculty of Health and Medical Sciences University of Copenhagen &

Become Our New Faculty Colleague! We are looking for a junior Principal Investigator to expand their stem cell research towards translational outcomes.
reNEW Copenhagen @ucph.bsky.social
#stemcell #diversity #faculty #regenerativemedicine shorturl.at/m9Zko

How Metabolism Can Shape Cells’ Destinies | Quanta Magazine A growing body of work suggests that cell metabolism — the chemical reactions that provide energy and building materials — plays a vital, overlooked role in the first steps of life.

It was very fun to contribute to this article: "But genes are not the whole story. New research has shown the extent to which cell metabolism (...) has an important, underappreciated role in directing cell fates". www.quantamagazine.org/how-metaboli... QuantaMagazine @ucph.bsky.social

Only 2 weeks left to apply! 16 fantastic positions available, also @ucph.bsky.social . For our project remember to apply both at shorturl.at/yf7Qq & nuclear-dn.eu.

We're hiring a motivated PhD student! Join reNEW @ucph.bsky.social & @nucleardn.bsky.social to study how metabolism regulates chromatin & stem cell fate thanks to generous Marie Skłodowska-Curie Fellowship. Remember to apply both at shorturl.at/yf7Qq & nuclear-dn.eu.

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.

I’m very excited about this collaborative project! We managed to significantly scale up and streamline human blastoid generation without the use of feeders. @leeboratory.bsky.social @grazianomartello.bsky.social @pasquelab.bsky.social and Nicolas Rivron @ucph.bsky.social

Congratulations!!! This is great news!!