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Reduced repression of cytokine signaling ameliorates age-induced decline in hematopoietic stem cell function.

Norddahl, Gudmundur LU ; Wahlestedt, Martin LU ; Gisler, Santiago; Sigvardsson, Mikael LU and Bryder, David LU (2012) In Aging Cell
Abstract
Aging causes profound effects on the hematopoietic stem cell (HSC) pool, including an altered output of mature progeny and enhanced self-propagation of repopulating-defective HSCs. An important outstanding question is whether HSCs can be protected from aging. The signal adaptor protein LNK negatively regulates hematopoiesis at several cellular stages. It has remained unclear how the enhanced sensitivity to cytokine signaling caused by LNK deficiency affects hematopoiesis upon aging. Our findings demonstrate that aged LNK(-/-) HSCs displayed a robust overall reconstitution potential and gave rise to a hematopoietic system with a balanced lineage distribution. Although aged LNK(-/-) HSCs displayed a distinct molecular profile in which... (More)
Aging causes profound effects on the hematopoietic stem cell (HSC) pool, including an altered output of mature progeny and enhanced self-propagation of repopulating-defective HSCs. An important outstanding question is whether HSCs can be protected from aging. The signal adaptor protein LNK negatively regulates hematopoiesis at several cellular stages. It has remained unclear how the enhanced sensitivity to cytokine signaling caused by LNK deficiency affects hematopoiesis upon aging. Our findings demonstrate that aged LNK(-/-) HSCs displayed a robust overall reconstitution potential and gave rise to a hematopoietic system with a balanced lineage distribution. Although aged LNK(-/-) HSCs displayed a distinct molecular profile in which reduced proliferation was central, little or no difference in the proliferation of aged LNK(-/-) HSCs was observed after transplantation when compared to aged WT HSCs. This coincided with equal telomere maintenance in WT and LNK(-/-) HSCs. Collectively, our studies suggest that enhanced cytokine signaling can counteract functional age-related HSC decline. © 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. (Less)
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published
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Aging Cell
publisher
Wiley-Blackwell
external identifiers
  • wos:000311113500024
  • pmid:22809070
  • scopus:84869186672
ISSN
1474-9726
DOI
10.1111/j.1474-9726.2012.00863.x
language
English
LU publication?
yes
id
8754e349-acc2-47ed-b52a-e580f1599721 (old id 2966958)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22809070?dopt=Abstract
date added to LUP
2012-08-09 19:41:48
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2017-07-23 04:54:37
@article{8754e349-acc2-47ed-b52a-e580f1599721,
  abstract     = {Aging causes profound effects on the hematopoietic stem cell (HSC) pool, including an altered output of mature progeny and enhanced self-propagation of repopulating-defective HSCs. An important outstanding question is whether HSCs can be protected from aging. The signal adaptor protein LNK negatively regulates hematopoiesis at several cellular stages. It has remained unclear how the enhanced sensitivity to cytokine signaling caused by LNK deficiency affects hematopoiesis upon aging. Our findings demonstrate that aged LNK(-/-) HSCs displayed a robust overall reconstitution potential and gave rise to a hematopoietic system with a balanced lineage distribution. Although aged LNK(-/-) HSCs displayed a distinct molecular profile in which reduced proliferation was central, little or no difference in the proliferation of aged LNK(-/-) HSCs was observed after transplantation when compared to aged WT HSCs. This coincided with equal telomere maintenance in WT and LNK(-/-) HSCs. Collectively, our studies suggest that enhanced cytokine signaling can counteract functional age-related HSC decline. © 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.},
  author       = {Norddahl, Gudmundur and Wahlestedt, Martin and Gisler, Santiago and Sigvardsson, Mikael and Bryder, David},
  issn         = {1474-9726},
  language     = {eng},
  month        = {07},
  publisher    = {Wiley-Blackwell},
  series       = {Aging Cell},
  title        = {Reduced repression of cytokine signaling ameliorates age-induced decline in hematopoietic stem cell function.},
  url          = {http://dx.doi.org/10.1111/j.1474-9726.2012.00863.x},
  year         = {2012},
}