We did it in cancer cell lines and validated the phenotype in cancer tissues

Not IN, they are compressing the nucleus from the outside ;)

Earlier this summer we have published this. Looks like a similar localization of mitochondria in the centre of the nucleus: www.nature.com/articles/s41...

Uncovering how mechanical forces can influence nuclear ATP levels, with downstream effects on DNA damage response and cell cycle progression.

#Mechanobiology #NuclearMetabolism #CellFate #DNArepair #CellCycle

BIG THANKS to everyone involved, especially Toni for his amazing work!

Thanks to our sponsors:
@ageinves.bsky.social
@ERC_Research #ERCStG EPICAMENTE
@crg.eu

Open questions:
Is nuclear metabolism linked to #aging?
Can we reverse the aging process by restoring nuclear metabolism?
What else besides PIP2?

If you are interested in answering these questions, please contact us!

Our study links nuclear PIP2 metabolism to nucleoli structure, histone modification, and cell cycle progression. This provides evidence that nuclear metabolism oscillations can control cell cycle progression, which, when altered, can induce cell cycle arrest and cell senescence.

4) The aberrant localization of PIP2 in the nucleus/nucleoli and the alteration of the nucleoli structure lead to changes in the accumulation of histone marks. For example, H4K20me1 decreases, which subsequently affects proper cell cycle progression.

3) What happens to cells when we interfere with PIP2 metabolism in the nucleus? In addition to preventing cell cycle progression, the structure of the nucleolus is affected and the localization of PIP2 to the Fibrillarin-labeled nucleoli region is altered.

2) We used our lab's gold standard chromatome protocol to study the oscillation of metabolic enzymes on chromatin during the cell cycle. We identified a correlation between cell cycle progression and PIP2 metabolism on chromatin.

1) By integrating FUCCI reporters and classical proliferation/senescent markers, we identified a population of cells, which we termed G0-senescent, that had never before been identified using FUCCI.

Our initial question was: does the cell cycle control the association of metabolic enzymes with chromatin? The short answer is YES!
We adapted the FUCCI system and extensively characterized U2OS FUCCI using HT-microscopy and FACS.

Open questions:
Is nuclear metabolism linked to aging?
Can we reverse the aging process by restoring nuclear metabolism?
What else besides PIP2?

If you are interested in answering these questions, please contact us!

Our study links nuclear PIP2 metabolism to nucleoli structure, histone modification, and cell cycle progression. This provides evidence that nuclear metabolism oscillations can control cell cycle progression, which, when altered, can induce cell cycle arrest and cell senescence.

4) The aberrant localization of PIP2 in the nucleus/nucleoli and the alteration of the nucleoli structure lead to changes in the accumulation of histone marks. For example, H4K20me1 decreases, which subsequently affects proper cell cycle progression.

3) What happens to cells when we interfere with PIP2 metabolism in the nucleus? In addition to preventing cell cycle progression, the structure of the nucleolus is affected and the localization of PIP2 to the Fibrillarin-labeled nucleoli region is altered.

2) We used our lab's gold standard chromatome protocol to study the oscillation of metabolic enzymes on chromatin during the cell cycle. We identified a correlation between cell cycle progression and PIP2 metabolism on chromatin.