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Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate

Author

Listed:
  • Martin Wahlestedt

    (Lund University, Medical Faculty, Institution for Laboratory Medicine)

  • Eva Erlandsson

    (Lund University, Medical Faculty, Institution for Laboratory Medicine)

  • Trine Kristiansen

    (Lund University, Medical Faculty, Institution for Laboratory Medicine)

  • Rong Lu

    (Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California)

  • Cord Brakebusch

    (Biotech Research and Innovation Centre, Biomedical Institute, University of Copenhagen
    Core Facility for Transgenic Mice, The Panum Institute)

  • Irving L. Weissman

    (Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University)

  • Joan Yuan

    (Lund University, Medical Faculty, Institution for Laboratory Medicine
    StemTherapy, Lund University)

  • Javier Martin-Gonzalez

    (Core Facility for Transgenic Mice, The Panum Institute)

  • David Bryder

    (Lund University, Medical Faculty, Institution for Laboratory Medicine
    StemTherapy, Lund University)

Abstract

Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic stem cell (HSC) ageing is linked to several functional shortcomings. However, besides the recent realization that individual HSCs might be preset differentially already from young age, HSCs might also age asynchronously. Evaluating the prospects for HSC rejuvenation therefore ultimately requires approaching those HSCs that are functionally affected by age. Here we combine genetic barcoding of aged murine HSCs with the generation of induced pluripotent stem (iPS) cells. This allows us to specifically focus on aged HSCs presenting with a pronounced lineage skewing, a hallmark of HSC ageing. Functional and molecular evaluations reveal haematopoiesis from these iPS clones to be indistinguishable from that associating with young mice. Our data thereby provide direct support to the notion that several key functional attributes of HSC ageing can be reversed.

Suggested Citation

  • Martin Wahlestedt & Eva Erlandsson & Trine Kristiansen & Rong Lu & Cord Brakebusch & Irving L. Weissman & Joan Yuan & Javier Martin-Gonzalez & David Bryder, 2017. "Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14533
    DOI: 10.1038/ncomms14533
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