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

Kyung Mok Kim, Anna Mura-Meszaros, Marie Tollot, Murali Shyam Krishnan, Marco Grundl, Laura Neubert, Marco Groth, Alejo Rodriguez-Fraticelli, Arthur Flohr Svendsen, Stefano Campaner, Nico Andreas, Thomas Kamradt, Steve Hoffmann, Fernando D. Camargo, Florian H. Heidel, Leonid Bystrykh, Gerald de Haan, Bjorn von Eyss*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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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.

Immune system function declines with age, a consequence of defects in hematopoietic stem cells (HSCs). Here the authors show that TAZ buffers age-related loss of PU.1 activity to maintain HSC functionality and identify the surface protein Clca3a1 as a marker of "young-like" HSCs, even in old mice.

Original languageEnglish
Article number5187
Number of pages16
JournalNature Communications
Issue number1
Publication statusPublished - 3-Sept-2022


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