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Reduced repression of cytokine signaling ameliorates age-induced decline in hematopoietic stem cell function
Lund University, Sweden .
Lund University, Sweden .
Lund University, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
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2012 (English)In: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 11, no 6, 1128-1131 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Blackwell Publishing , 2012. Vol. 11, no 6, 1128-1131 p.
Keyword [en]
aging, cytokine signaling, hematopoiesis, hematopoietic stem cells, LNK, telomeres
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-86645DOI: 10.1111/j.1474-9726.2012.00863.xISI: 000311113500024OAI: diva2:580099

Funding Agencies|Swedish Cancer Foundation||Swedish Medical Research Council||Swedish Pediatric Leukemia Foundation||

Available from: 2012-12-20 Created: 2012-12-20 Last updated: 2012-12-20

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Sigvardsson, Mikael
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Experimental HematologyFaculty of Health Sciences
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