Open AccessReduced repression of cytokine signaling ameliorates age‐induced decline in hematopoietic stem cell function
Author(s) -
Norddahl Gudmundur L.,
Wahlestedt Martin,
Gisler Santiago,
Sigvardsson Mikael,
Bryder David
Publication year - 2012
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2012.00863.x
Subject(s) - haematopoiesis , biology , stem cell , microbiology and biotechnology , hematopoietic stem cell , cytokine , signal transducing adaptor protein , immunology , signal transduction , psychological repression , cancer research , genetics , gene expression , gene
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.