And follow the live stream if you can’t make it in person tapahtumat.helsinki.fi/en-FI/page/6...

Read the thesis here helda.helsinki.fi/items/477af6...

And read the thesis helda.helsinki.fi/items/67fd7e...

Follow the live stream here tapahtumat.helsinki.fi/en-FI/page/6...

@natmetabolism.nature.com

Also read the news item by Uni Helsinki, descibing possible future application of the findings during chemothrapy-induced damage www.helsinki.fi/en/hilife-he... 8/8 @helsinki-biotech.bsky.social

Congratulations to Simon @simonsterson.bsky.social, for fantastic persistence during the whole journey, and big thank you to all co-authors, @hienbui.bsky.social Arto Viitanen @hietakangaslab.bsky.social @pekka-katajisto.bsky.social and others @metastem.bsky.social @helsinki.fi 7/8

Our results demonstrate the existence of previously unknown asymmetric division and metabolic heterogeneity in the intestinal stem cell pool, which can’t be seen in the transcriptome. Further, we find that metabolic intervention can be used for replacement of specific defective cells. 6/8

aKG supplementation in vivo leads to renewal of Paneth cells, which in old animals reduces expression of the Wnt-antagonist Notum, and rescues recovery after 5-FU-induced damage to the level of young animals. 5/8

ISCs with old mitochondria have faster TCA-cycle turnover and higher amounts of aKG, which drives the bias towards the Paneth cell linage and increased Tet2-dependent 5-hydroxy methylation of cytosines in DNA. 4/8

These stem cells (ISC-mito-O) are better at forming organoids in vitro due to their ability to regenerate Paneth cells faster. 3/8

Using in vivo snap-tag labeling of mitochondrial age-classes, we found that the intestine contains a subset of stem cells that retain old mitochondria through asymmetric division. 2/8

Thank you Christian 😊