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Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells

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  • Johanna Flach

    (The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco
    Institute of Experimental Cancer Research, Comprehensive Cancer Center, 89081 Ulm, Germany)

  • Sietske T. Bakker

    (The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco)

  • Mary Mohrin

    (The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco)

  • Pauline C. Conroy

    (Center for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway)

  • Eric M. Pietras

    (The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco)

  • Damien Reynaud

    (The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco)

  • Silvia Alvarez

    (Spanish National Cancer Research Centre (CNIO), E-28049 Madrid, Spain)

  • Morgan E. Diolaiti

    (University of California San Francisco)

  • Fernando Ugarte

    (Institute for the Biology of Stem Cells, University of California Santa Cruz)

  • E. Camilla Forsberg

    (Institute for the Biology of Stem Cells, University of California Santa Cruz)

  • Michelle M. Le Beau

    (Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago)

  • Bradley A. Stohr

    (University of California San Francisco)

  • Juan Méndez

    (Spanish National Cancer Research Centre (CNIO), E-28049 Madrid, Spain)

  • Ciaran G. Morrison

    (Center for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway)

  • Emmanuelle Passegué

    (The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco)

Abstract

Haematopoietic stem cell (HSC) function is known to degrade with age; here, replication stress is shown to be a potent driver of the functional decline of HSCs during physiological ageing in mice due to decreased expression of mini-chromosome maintenance helicase components and reduced activity of the DNA replication machinery.

Suggested Citation

  • Johanna Flach & Sietske T. Bakker & Mary Mohrin & Pauline C. Conroy & Eric M. Pietras & Damien Reynaud & Silvia Alvarez & Morgan E. Diolaiti & Fernando Ugarte & E. Camilla Forsberg & Michelle M. Le Be, 2014. "Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells," Nature, Nature, vol. 512(7513), pages 198-202, August.
    • Handle: RePEc:nat:nature:v:512:y:2014:i:7513:d:10.1038_nature13619
    DOI: 10.1038/nature13619
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    Cited by:

    1. Maria Thürmer & André Gollowitzer & Helmut Pein & Konstantin Neukirch & Elif Gelmez & Lorenz Waltl & Natalie Wielsch & René Winkler & Konstantin Löser & Julia Grander & Madlen Hotze & Sönke Harder & A, 2022. "PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. 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.
    3. Pradeep Ramalingam & Michael C. Gutkin & Michael G. Poulos & Taylor Tillery & Chelsea Doughty & Agatha Winiarski & Ana G. Freire & Shahin Rafii & David Redmond & Jason M. Butler, 2023. "Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response," Nature Communications, Nature, vol. 14(1), pages 1-20, 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. Karl-Heinz Tomaszowski & Sunetra Roy & Carolina Guerrero & Poojan Shukla & Caezaan Keshvani & Yue Chen & Martina Ott & Xiaogang Wu & Jianhua Zhang & Courtney D. DiNardo & Detlev Schindler & Katharina , 2023. "Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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