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

Martin Wahlestedt1, Eva Erlandsson1, Trine Kristiansen1

  • 1Lund University, Medical Faculty, Institution for Laboratory Medicine, Division of Molecular Hematology, Klinikgatan 26, BMC B12, 221 84 Lund, Sweden.

Nature Communications
|February 23, 2017
PubMed

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.

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