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Publication : Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice.

First Author  Song Z Year  2010
Journal  Blood Volume  115
Issue  8 Pages  1481-9
PubMed ID  19965646 Mgi Jnum  J:157779
Mgi Id  MGI:4436962 Doi  10.1182/blood-2009-08-237230
Citation  Song Z, et al. (2010) Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice. Blood 115(8):1481-9
abstractText  There is growing evidence that telomere dysfunction can contribute to human aging. Telomere dysfunction limits lymphopoiesis in aging telomerase knockout (mTerc(-/-)) mice primarily by the induction of stem cell-extrinsic alterations. The relative contribution of alterations in the stem cell niche and the systemic environment to the impairment of lymphopoiesis in response to telomere dysfunction is currently unknown. This study reveals a minor impact of stem cell-intrinsic defects on the impairment of B and T lymphopoiesis in response to telomere dysfunction. The impairment in B and T lymphopoiesis in aging telomere-dysfunctional mice was mainly due to alterations of the systemic environment. Telomere dysfunction had no significant cell-autonomous effects impairing the function of thymic or bone marrow niches in supporting B and T lymphopoiesis. Moreover, age-related alterations in the cellular composition of the thymic epithelium in telomere-dysfunctional mice were rescued by transplantation of the thymus into a wild-type environment; these rejuvenated thymi supported normal T lymphopoiesis in recipient mice. Together, these data place alterations in the systemic environment on top of the hierarchy of events limiting lymphopoiesis in response to telomere dysfunction.
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