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

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 Beau, Bradley A. Stohr, Juan Méndez, Ciaran G. Morrison and Emmanuelle Passegué ()
Additional contact information
Johanna Flach: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco
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

Nature, 2014, vol. 512, issue 7513, 198-202

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.

Date: 2014
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DOI: 10.1038/nature13619

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