Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate
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Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate. / Wahlestedt, Martin; Erlandsson, Eva; Kristiansen, Trine; Lu, Rong; Brakebusch, Cord Herbert; Weissman, Irving L; Yuan, Joan; Martin-Gonzalez, Javier; Bryder, David.
In: Nature Communications, Vol. 8, 14533, 22.02.2017.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 14533
ER -
ID: 174273712