Reduced repression of cytokine signaling ameliorates age‐induced decline in hematopoietic stem cell function |
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Authors: | Gudmundur L. Norddahl Martin Wahlestedt Santiago Gisler Mikael Sigvardsson David Bryder |
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Affiliation: | 1. Lund University, Institution for Experimental Medical Science, Immunology section, BMC D14, Tornav?gen 10, 221 84 Lund, Sweden;2. Link?ping University, Department of Clinical and Experimental Medicine, Sandb?cksgatan 7, 581 83 Link?ping, Sweden |
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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. |
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Keywords: | aging cytokine signaling hematopoiesis hematopoietic stem cells LNK telomeres |
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