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Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity

Author

Listed:
  • Kyung Mok Kim

    (Fritz Lipmann Institute e.V.)

  • Anna Mura-Meszaros

    (Fritz Lipmann Institute e.V.)

  • Marie Tollot

    (Fritz Lipmann Institute e.V.)

  • Murali Shyam Krishnan

    (Fritz Lipmann Institute e.V.)

  • Marco Gründl

    (Fritz Lipmann Institute e.V.)

  • Laura Neubert

    (Fritz Lipmann Institute e.V.)

  • Marco Groth

    (Fritz Lipmann Institute e.V.)

  • Alejo Rodriguez-Fraticelli

    (Barcelona Institute of Science and Technology (BIST)
    Boston Children’s Hospital
    Harvard University)

  • Arthur Flohr Svendsen

    (University of Groningen)

  • Stefano Campaner

    (Fondazione Istituto Italiano di Tecnologia (IIT))

  • Nico Andreas

    (Jena University Hospital)

  • Thomas Kamradt

    (Jena University Hospital)

  • Steve Hoffmann

    (Fritz Lipmann Institute e.V.)

  • Fernando D. Camargo

    (Barcelona Institute of Science and Technology (BIST))

  • Florian H. Heidel

    (Fritz Lipmann Institute e.V.
    Jena University Hospital
    Innere Medizin C, Universitätsmedizin Greifswald, Sauerbruchstrasse)

  • Leonid V. Bystrykh

    (University of Groningen)

  • Gerald Haan

    (University of Groningen
    University of Amsterdam)

  • Björn Eyss

    (Fritz Lipmann Institute e.V.)

Abstract

Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, as we age, the immune system shows a functional decline that can be attributed in large part to age-associated defects in hematopoietic stem cells (HSCs)—the cells at the apex of the immune cell hierarchy. Here, we find that the Hippo pathway coactivator TAZ is potently induced in old HSCs and protects these cells from functional decline. We identify Clca3a1 as a TAZ-induced gene that allows us to trace TAZ activity in vivo. Using CLCA3A1 as a marker, we can isolate “young-like” HSCs from old mice. Mechanistically, Taz acts as coactivator of PU.1 and to some extent counteracts the gradual loss of PU.1 expression during HSC aging. Our work thus uncovers an essential role for Taz in a previously undescribed fail-safe mechanism in aging HSCs.

Suggested Citation

  • Kyung Mok Kim & Anna Mura-Meszaros & Marie Tollot & Murali Shyam Krishnan & Marco Gründl & Laura Neubert & Marco Groth & Alejo Rodriguez-Fraticelli & Arthur Flohr Svendsen & Stefano Campaner & Nico An, 2022. "Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32970-1
    DOI: 10.1038/s41467-022-32970-1
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    References listed on IDEAS

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    1. Tsu-Yi Su & Julia Hauenstein & Ece Somuncular & Özge Dumral & Elory Leonard & Charlotte Gustafsson & Efthymios Tzortzis & Aurora Forlani & Anne-Sofie Johansson & Hong Qian & Robert Månsson & Sidinh Lu, 2024. "Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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