IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32970-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32970-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32970-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alejo E. Rodriguez-Fraticelli & Caleb Weinreb & Shou-Wen Wang & Rosa P. Migueles & Maja Jankovic & Marc Usart & Allon M. Klein & Sally Lowell & Fernando D. Camargo, 2020. "Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis," Nature, Nature, vol. 583(7817), pages 585-589, July.
    2. Theodore T. Ho & Matthew R. Warr & Emmalee R. Adelman & Olivia M. Lansinger & Johanna Flach & Evgenia V. Verovskaya & Maria E. Figueroa & Emmanuelle Passegué, 2017. "Autophagy maintains the metabolism and function of young and old stem cells," Nature, Nature, vol. 543(7644), pages 205-210, March.
    3. Dana Elster & Marie Tollot & Karin Schlegelmilch & Alessandro Ori & Andreas Rosenwald & Erik Sahai & Björn von Eyss, 2018. "TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    4. Alex Gregorieff & Yu Liu & Mohammad R. Inanlou & Yuliya Khomchuk & Jeffrey L. Wrana, 2015. "Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer," Nature, Nature, vol. 526(7575), pages 715-718, October.
    5. Maria Carolina Florian & Kalpana J. Nattamai & Karin Dörr & Gina Marka & Bettina Überle & Virag Vas & Christina Eckl & Immanuel Andrä & Matthias Schiemann & Robert A. J. Oostendorp & Karin Scharffette, 2013. "A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing," Nature, Nature, vol. 503(7476), pages 392-396, November.
    6. Arshad Ayyaz & Sandeep Kumar & Bruno Sangiorgi & Bibaswan Ghoshal & Jessica Gosio & Shaida Ouladan & Mardi Fink & Seda Barutcu & Daniel Trcka & Jess Shen & Kin Chan & Jeffrey L. Wrana & Alex Gregorief, 2019. "Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell," Nature, Nature, vol. 569(7754), pages 121-125, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Clara Morral & Arshad Ayyaz & Hsuan-Cheng Kuo & Mardi Fink & Ioannis I. Verginadis & Andrea R. Daniel & Danielle N. Burner & Lucy M. Driver & Sloane Satow & Stephanie Hasapis & Reem Ghinnagow & Lixia , 2024. "p53 promotes revival stem cells in the regenerating intestine after severe radiation injury," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Marco Calafiore & Ya-Yuan Fu & Paola Vinci & Viktor Arnhold & Winston Y. Chang & Suze A. Jansen & Anastasiya Egorova & Shuichiro Takashima & Jason Kuttiyara & Takahiro Ito & Jonathan Serody & Susumu N, 2023. "A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Humberto Contreras-Trujillo & Jiya Eerdeng & Samir Akre & Du Jiang & Jorge Contreras & Basia Gala & Mary C. Vergel-Rodriguez & Yeachan Lee & Aparna Jorapur & Areen Andreasian & Lisa Harton & Charles S, 2021. "Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Tsunaki Higa & Yasutaka Okita & Akinobu Matsumoto & Shogo Nakayama & Takeru Oka & Osamu Sugahara & Daisuke Koga & Shoichiro Takeishi & Hirokazu Nakatsumi & Naoki Hosen & Sylvie Robine & Makoto M. Take, 2022. "Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Mina N. F. Morcos & Congxin Li & Clara M. Munz & Alessandro Greco & Nicole Dressel & Susanne Reinhardt & Katrin Sameith & Andreas Dahl & Nils B. Becker & Axel Roers & Thomas Höfer & Alexander Gerbaule, 2022. "Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Sara M. Parigi & Ludvig Larsson & Srustidhar Das & Ricardo O. Ramirez Flores & Annika Frede & Kumar P. Tripathi & Oscar E. Diaz & Katja Selin & Rodrigo A. Morales & Xinxin Luo & Gustavo Monasterio & C, 2022. "The spatial transcriptomic landscape of the healing mouse intestine following damage," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Laura Solé & Teresa Lobo-Jarne & Daniel Álvarez-Villanueva & Josune Alonso-Marañón & Yolanda Guillén & Marta Guix & Irene Sangrador & Catalina Rozalén & Anna Vert & Antonio Barbachano & Joan Lop & Mar, 2022. "p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Manqiang Lin & Kimberly Hartl & Julian Heuberger & Giulia Beccaceci & Hilmar Berger & Hao Li & Lichao Liu & Stefanie Müllerke & Thomas Conrad & Felix Heymann & Andrew Woehler & Frank Tacke & Nikolaus , 2023. "Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Wenjuan Zhang & Bowei Zhou & Xiao Yang & Jin Zhao & Jingjuan Hu & Yuqi Ding & Shuteng Zhan & Yifeng Yang & Jun Chen & Fu Zhang & Bingcheng Zhao & Fan Deng & Zebin Lin & Qishun Sun & Fangling Zhang & Z, 2023. "Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Scott R. Tyler & Daniel Lozano-Ojalvo & Ernesto Guccione & Eric E. Schadt, 2024. "Anti-correlated feature selection prevents false discovery of subpopulations in scRNAseq," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Xin-yu He & Xiao Fan & Lei Qu & Xiang Wang & Li Jiang & Ling-jie Sang & Cheng-yu Shi & Siyi Lin & Jie-cheng Yang & Zuo-zhen Yang & Kai Lei & Jun-hong Li & Huai-qiang Ju & Qingfeng Yan & Jian Liu & Fud, 2023. "LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Kathleen Shah & Muralidhara Rao Maradana & M. Joaquina Delàs & Amina Metidji & Frederike Graelmann & Miriam Llorian & Probir Chakravarty & Ying Li & Mauro Tolaini & Michael Shapiro & Gavin Kelly & Chr, 2022. "Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Jong Hoon Won & Jacob S. Choi & Joon-Il Jun, 2022. "CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Yumin Liu & Linjuan Shi & Yifan Chen & Sifan Luo & Yuehang Chen & Hongtian Chen & Wenlang Lan & Xun Lu & Zhan Cao & Zehua Ye & Jinping Li & Bo Yu & Elaine Dzierzak & Zhuan Li, 2024. "Autophagy regulates the maturation of hematopoietic precursors in the embryo," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Yan Gu & Yanrong Chen & Lai Wei & Shuang Wu & Kaicheng Shen & Chengxiang Liu & Yan Dong & Yang Zhao & Yue Zhang & Chi Zhang & Wenling Zheng & Jiangyi He & Yunlong Wang & Yifei Li & Xiaoxin Zhao & Hong, 2021. "ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    16. Jos Urbanus & Jason Cosgrove & Joost B. Beltman & Yuval Elhanati & Rafael A. Moral & Cecile Conrad & Jeroen W. Heijst & Emilie Tubeuf & Arno Velds & Lianne Kok & Candice Merle & Jens P. Magnusson & Lé, 2023. "DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    17. Mara Martín-Alonso & Sharif Iqbal & Pia M. Vornewald & Håvard T. Lindholm & Mirjam J. Damen & Fernando Martínez & Sigrid Hoel & Alberto Díez-Sánchez & Maarten Altelaar & Pekka Katajisto & Alicia G. Ar, 2021. "Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    18. Jina Yun & Simon Hansen & Otto Morris & David T. Madden & Clare Peters Libeu & Arjun J. Kumar & Cameron Wehrfritz & Aaron H. Nile & Yingnan Zhang & Lijuan Zhou & Yuxin Liang & Zora Modrusan & Michelle, 2023. "Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    19. Gustavo Medeiros & Raphael Ortiz & Petr Strnad & Andrea Boni & Franziska Moos & Nicole Repina & Ludivine Challet Meylan & Francisca Maurer & Prisca Liberali, 2022. "Multiscale light-sheet organoid imaging framework," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Zihua Yu & Yuedan Zhu & Yi Chen & Chenxi Feng & Zehong Zhang & Xiaoxin Guo & Haiou Chen & Xingzhu Liu & Yu Yuan & Haiyang Chen, 2024. "Nutrient-sensing alteration leads to age-associated distortion of intestinal stem cell differentiating direction," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32970-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.