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Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells

Author

Listed:
  • Dagmar Walter

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany)

  • Amelie Lier

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany)

  • Anja Geiselhart

    (Deutsches Krebsforschungszentrum (DKFZ), Experimental Hematology Group, 69120 Heidelberg, Germany)

  • Frederic B. Thalheimer

    (Goethe University Frankfurt, 60595 Frankfurt am Main, Germany)

  • Sina Huntscha

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany)

  • Mirko C. Sobotta

    (Deutsches Krebsforschungszentrum (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany)

  • Bettina Moehrle

    (Institute for Molecular Medicine, Stem Cells and Aging, Ulm University, 89081 Ulm, Germany)

  • David Brocks

    (Deutsches Krebsforschungszentrum (DKFZ), Experimental Hematology Group, 69120 Heidelberg, Germany)

  • Irem Bayindir

    (Deutsches Krebsforschungszentrum (DKFZ), Experimental Hematology Group, 69120 Heidelberg, Germany)

  • Paul Kaschutnig

    (Deutsches Krebsforschungszentrum (DKFZ), Experimental Hematology Group, 69120 Heidelberg, Germany)

  • Katja Muedder

    (Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany)

  • Corinna Klein

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany)

  • Anna Jauch

    (Institute of Human Genetics, University of Heidelberg, 69120 Heidelberg, Germany)

  • Timm Schroeder

    (ETH Zurich, 4058 Basel, Switzerland)

  • Hartmut Geiger

    (Institute for Molecular Medicine, Stem Cells and Aging, Ulm University, 89081 Ulm, Germany
    Cincinnati Children’s Hospital Medical Center)

  • Tobias P. Dick

    (Deutsches Krebsforschungszentrum (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany)

  • Tim Holland-Letz

    (Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany)

  • Peter Schmezer

    (Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany)

  • Steven W. Lane

    (QIMR Berghofer Medical Research Institute, University of Queensland, Brisbane 4006, Australia)

  • Michael A. Rieger

    (Goethe University Frankfurt, 60595 Frankfurt am Main, Germany)

  • Marieke A. G. Essers

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany
    Deutsches Krebsforschungszentrum (DKFZ), Hematopoietic Stem Cells and Stress Group, 69120 Heidelberg, Germany)

  • David A. Williams

    (Boston Children’s Hospital
    Dana-Faber Cancer Institute
    Harvard Stem Cell Institute
    Harvard Medical School)

  • Andreas Trumpp

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany
    Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany)

  • Michael D. Milsom

    (Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (HI-STEM), 69120 Heidelberg, Germany
    Deutsches Krebsforschungszentrum (DKFZ), Experimental Hematology Group, 69120 Heidelberg, Germany)

Abstract

Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system.

Suggested Citation

  • Dagmar Walter & Amelie Lier & Anja Geiselhart & Frederic B. Thalheimer & Sina Huntscha & Mirko C. Sobotta & Bettina Moehrle & David Brocks & Irem Bayindir & Paul Kaschutnig & Katja Muedder & Corinna K, 2015. "Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells," Nature, Nature, vol. 520(7548), pages 549-552, April.
    • Handle: RePEc:nat:nature:v:520:y:2015:i:7548:d:10.1038_nature14131
    DOI: 10.1038/nature14131
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    Cited by:

    1. Elliot H. Akama-Garren & Theo Broek & Lea Simoni & Carlos Castrillon & Cees E. Poel & Michael C. Carroll, 2021. "Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Mohankrishna Dalvoy Vasudevarao & Denise Posadas Pena & Michaela Ihle & Chiara Bongiovanni & Pallab Maity & Dominik Geissler & Hossein Falah Mohammadi & Melanie Rall-Scharpf & Julian Niemann & Mathild, 2025. "BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    3. Narasaiah Kovuru & Makiko Mochizuki-Kashio & Theresa Menna & Greer Jeffrey & Yuning Hong & Young me Yoon & Zhe Zhang & Peter Kurre, 2024. "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Jacqueline Feyen & Zhen Ping & Lanpeng Chen & Claire Dijk & Tim V. D. Tienhoven & Paulina M. H. Strien & Remco M. Hoogenboezem & Michiel J. W. Wevers & Mathijs A. Sanders & Ivo P. Touw & Marc H. G. P., 2022. "Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Kim Vanuytsel & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Zhe Wang & Wilfredo F. Garcia-Beltran & Vladimir Vrbanac & Dylan Parsons & Evan C. Lam & Taylor M. Matte & Todd W. Dowrey & Sara, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Carla Umansky & Agustín E. Morellato & Matthias Rieckher & Marco A. Scheidegger & Manuela R. Martinefski & Gabriela A. Fernández & Oleg Pak & Ksenia Kolesnikova & Hernán Reingruber & Mariela Bollini &, 2022. "Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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