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

Martin Wahlestedt, Eva Erlandsson, Trine Kristiansen, Rong Lu, Cord Brakebusch, Irving L. Weissman, Joan Yuan, Javier Martin-Gonzalez and David Bryder ()
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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
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
Javier Martin-Gonzalez: Core Facility for Transgenic Mice, The Panum Institute
David Bryder: Lund University, Medical Faculty, Institution for Laboratory Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14533

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