title: Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice.
abstract: 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.
authors: Institute of Molecular Medicine and Max-Planck-Research Group on Stem Cell Aging, University of Ulm, Ulm, Germany;
authors: Zhangfa
authors: Z
authors: Song
authors: Jianwei
authors: J
authors: Wang
authors: Luis Miguel
authors: LM
authors: Guachalla
authors: Grzegorz
authors: G
authors: Terszowski
authors: Hans-Reimer
authors: HR
authors: Rodewald
authors: Zhenyu
authors: Z
authors: Ju
authors: K Lenhard
authors: KL
authors: Rudolph
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D004848:Epithelium / Q000201:enzymology; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology* / Q000235:genetics; D013950:Thymus Gland / Q000201:enzymology / Q000637:transplantation
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase