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

Aging Cell

Gudmundur L. Norddahl¹  Martin Wahlestedt¹  Santiago Gisler¹  Mikael Sigvardsson² 

[1]Lund University, Institution for Experimental Medical Science, Immunology section, BMC D14, Tornavägen 10, 221 84 Lund, Sweden

[2]Linköping University, Department of Clinical and Experimental Medicine, Sandbäcksgatan 7, 581 83 Linköping, Sweden

关键词: aging;    cytokine signaling;    hematopoiesis;    hematopoietic stem cells;    LNK;    telomeres;   

DOI  :  10.1111/j.1474-9726.2012.00863.x

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland