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

TY - JOUR

T1 - Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate

AU - Wahlestedt, Martin

AU - Erlandsson, Eva

AU - Kristiansen, Trine

AU - Lu, Rong

AU - Brakebusch, Cord Herbert

AU - Weissman, Irving L

AU - Yuan, Joan

AU - Martin-Gonzalez, Javier

AU - Bryder, David

PY - 2017/2/22

Y1 - 2017/2/22

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/ncomms14533

DO - 10.1038/ncomms14533

M3 - Journal article

C2 - 28224997

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 14533

ER -