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KatajistoLab

@katajistolab.bsky.social

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Lab of Pekka Katajisto @pekka-katajisto.bsky.social at University of Helsinki and Karolinska Institutet. We study stem cells, aging, metabolism, organelle age and niche interactions https://www.katajisto-lab.com

www.katajisto-lab.com

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KatajistoLab @katajistolab.bsky.social · Jul 14

Proudly presenting Simon’s @simonsterson.bsky.social‬ paper on asymmetric apportioning of old mitochondria biasing intestinal stem cells for the Paneth cell linage through aKG-dependent metabolism
@naturemetabolism.bsky.social www.nature.com/articles/s42... @helsinki.fi @metastem.bsky.social 🧵1/8

Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells - Nature Metabolism

Andersson et al. show that intestinal stem cells enriched for old mitochondria are metabolically distinct and have enhanced ability to regenerate the epithelial niche.

www.nature.com

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KatajistoLab @katajistolab.bsky.social · 7d

Check out the symposium organized by our CoE, excited to have Marcia Haigis, @lydiafinley.bsky.social, Matthias Hebrok and Tom MacVicar over in Helsinki in November. Sign up by October 22nd 👇

MetaStem @metastem.bsky.social · 7d

Excited to announce our Stem Cell Metabolism Symposium organized in Helsinki on November 12th. Fantastic invited speakers Marcia Haigis, Lydia Finley, Matthias Hebrok and Tom MacVicar. Sign up by Oct 22nd, free of charge, welcome! @hilife-helsinki.bsky.social @helsinki.fi @stemmprogram.bsky.social

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Reposted by KatajistoLab

MetaStem @metastem.bsky.social · 14d

Welcome to the Stem Cell Seminar next week Friday Oct 3rd at 9-11, ☕️🍪 at 8:30. Exciting science on embryo development, ECM, cancer and stem cells by Juha Kere and @johannaienglund.bsky.social labs. See you there! @hilife-helsinki.bsky.social @helsinki-biotech.bsky.social @stemmprogram.bsky.social

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Reposted by KatajistoLab

cniostopcancer.bsky.social @cniostopcancer.bsky.social · 27d

#CFM_MolCellAging: The third session will deal with the regulation of aging processes, with talks by
@pekka-katajisto.bsky.social @metastem.bsky.social @helsinki.fi and Salvador Aznar @irbbarcelona.org

Registration: http://bit.ly/4kOyYch

🤝With support of @caixaresearch.bsky.social

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Reposted by KatajistoLab

Craig Primmer @fishcongen.bsky.social · Sep 5

Pekka Katajisto @katajistolab.bsky.social introducing Nobel laureate Shinya Yamanaka who will talk about 2 of my favorite topics: sciences and marathons

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KatajistoLab @katajistolab.bsky.social · Jul 15

@natmetabolism.nature.com

KatajistoLab @katajistolab.bsky.social · Jul 15

Also read the research briefing on our latest paper in @natmetabolism.nature.com

Nature Metabolism @natmetabolism.nature.com · Jul 15

Mitochondrial age-classes expand the heterogeneity of tissue-resident stem cells

Nature Metabolism, Published online: 14 July 2025; doi:10.1038/s42255-025-01326-6During cell division, a subset of intestinal stem cells (ISCs) inherits old mitochondria that increase intracellular α-ketoglutarate levels. α-Ketoglutarate facilitates remodelling of DNA methylation and boosts the ability of ISCs to regenerate the stem cell niche. Metabolite intervention with α-ketoglutarate during ageing can replace defective niche cells and enhance regeneration.

bit.ly

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Reposted by KatajistoLab

Nature Metabolism @natmetabolism.nature.com · Jul 15

Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells

Nature Metabolism, Published online: 14 July 2025; doi:10.1038/s42255-025-01325-7Andersson et al. show that intestinal stem cells enriched for old mitochondria are metabolically distinct and have enhanced ability to regenerate the epithelial niche.

bit.ly

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KatajistoLab @katajistolab.bsky.social · Jul 14

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

New Type of Intestinal Stem Cell Discovered, Offering Hope for Enhanced Regeneration and Chemotherapy Recovery | HiLIFE – Helsinki Institute of Life Science | University of Helsinki

A team of researchers from the University of Helsinki has discovered a previously unknown type of intestinal stem cell, which supports intestinal regeneration through its metabolically distinct mitoch...

www.helsinki.fi

KatajistoLab @katajistolab.bsky.social · Jul 14

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

KatajistoLab @katajistolab.bsky.social · Jul 14

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

KatajistoLab @katajistolab.bsky.social · Jul 14

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

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KatajistoLab @katajistolab.bsky.social · Jul 14

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

KatajistoLab @katajistolab.bsky.social · Jul 14

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

KatajistoLab @katajistolab.bsky.social · Jul 14

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

KatajistoLab @katajistolab.bsky.social · Jul 14

Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells - Nature Metabolism

Andersson et al. show that intestinal stem cells enriched for old mitochondria are metabolically distinct and have enhanced ability to regenerate the epithelial niche.

www.nature.com

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KatajistoLab @katajistolab.bsky.social · May 15

Thank you to the organizers of the fantastic meeting #CSMetabolites2025 Kivanc Birsoy @robzonculab.bsky.social and @cellpress.bsky.social editors Allyson Evans @kristabledsoe.bsky.social We had a fantastic time in Sitges, looking forward to this meeting happening again! @cellpressevents.bsky.social

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KatajistoLab @katajistolab.bsky.social · Apr 29

Thank you Christian 😊

KatajistoLab @katajistolab.bsky.social · Apr 28

ki.fi

KatajistoLab @katajistolab.bsky.social · Apr 28

Congratulations Hien Bui who showed remarkable persistence in initiating, leading and finalizing the project. Thank you to everyone involved, especially second authors @simonsterson.bsky.social Agustin Sola Carvajal and all collaborators at @helsinki.fi i.fi @metastem.bsky.social and @ki.se. 9/9

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KatajistoLab @katajistolab.bsky.social · Apr 28

In conclusion, we discovered a new role for peroxisomes in determination of cell fate of adult stem cells through their age-dependent segregation and spatially compartmentalized metabolism. The SNAP-PTS1 mouse will be a valuable tool for studying peroxisomal heterogeneity also in other tissues. 8/9

KatajistoLab @katajistolab.bsky.social · Apr 28

We found that sub-cellular compartmentalization of specific metabolic reactions determines cell fate as expression of G6PD specifically on the peroxisome membrane, but not in the cytosol or in the peroxisome matrix, boosted stemness through peroxisomal ether lipid synthesis. 7/9

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KatajistoLab @katajistolab.bsky.social · Apr 28

To find the mechanism, we performed proteomics of old and young peroxisomes isolated by density centrifugation and single-organelle FACS and found the metabolic enzyme G6PD to be enriched on old peroxisomes. 6/9

KatajistoLab @katajistolab.bsky.social · Apr 28

Similarly, during in vivo ACD of epidermal stem cells, old peroxisomes were preferentially inherited by the daughter cell that remains attached to the basement membrane. 5/9

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KatajistoLab @katajistolab.bsky.social · Apr 28

In in vitro ACD of basal mammary epithelial cells, daughter cells with old peroxisomes PO exhibited higher self-renewal and bi-potency than daughter cells with young peroxisomes PY, demonstrated by their ability to form organoids and create the luminal lineage to induce branching morphogenesis. 4/9

KatajistoLab @katajistolab.bsky.social · Apr 28

To study if this takes place in primary adult stem and progenitor cells, we generated a novel mouse model expressing the SNAP-PTS1 construct, allowing for temporal labelling of peroxisomes in vivo, and saw heterogeneity of peroxisome age in epithelial cells in the mammary gland and the skin. 3/9