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

Wahlestedt, Martin LU ; Erlandsson, Eva LU ; Kristiansen, Trine LU ; Lu, Rong; Brakebusch, Cord LU ; Weissman, Irving L.; Yuan, Joan LU ; Martin-Gonzalez, Javier and Bryder, David LU (2017) In Nature Communications 8.
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... (More)

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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organization
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type
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publication status
published
subject
in
Nature Communications
volume
8
publisher
Nature Publishing Group
external identifiers
  • scopus:85013408064
  • wos:000394737800001
ISSN
2041-1723
DOI
10.1038/ncomms14533
language
English
LU publication?
yes
id
3c640ece-3288-4380-bf7f-23e9afdef8af
date added to LUP
2017-03-08 10:00:30
date last changed
2018-01-07 11:54:32
@article{3c640ece-3288-4380-bf7f-23e9afdef8af,
  abstract     = {<p>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.</p>},
  articleno    = {14533},
  author       = {Wahlestedt, Martin and Erlandsson, Eva and Kristiansen, Trine and Lu, Rong and Brakebusch, Cord and Weissman, Irving L. and Yuan, Joan and Martin-Gonzalez, Javier and Bryder, David},
  issn         = {2041-1723},
  language     = {eng},
  month        = {02},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate},
  url          = {http://dx.doi.org/10.1038/ncomms14533},
  volume       = {8},
  year         = {2017},
}