Kared, HassenTan, Shu WenLau, Mai ChanChevrier, MarionTan, CrystalHow, WilsonWong, GlennStrickland, MarieMalleret, BenoitAmoah, AmandaPilipow, KarolinaZanon, VeronicaGovern, Naomi McLum, JosephineChen, Jin MiaoLee, BernettFlorian, Maria CarolinaGeiger, HartmutGinhoux, FlorentRuiz-Mateos, EzequielFulop, TamasRajasuriar, ReenaKamarulzaman, AdeebaNg, Tze PinLugli, EnricoLarbi, Anis2022-08-012022-08-012020-02-10Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al. Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway. Nat Commun. 2020 Feb 10;11(1):821http://hdl.handle.net/10668/3859The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Memory T cellsWnt signaling pathwayFlow cytometryImmune systemCateninsCélulas T de memoriaVía de señalización wntCitometría de flujoSistema inmunológicoCateninasMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::AgingMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Biological Factors::AntigensMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-LymphocytesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression ProfilingMedical Subject Headings::Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV InfectionsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic MemoryMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and ProteinsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Anatomy::Cells::Stem Cells::Hematopoietic Stem Cells::Lymphoid Progenitor Cells::Precursor Cells, T-LymphoidMedical Subject Headings::Anatomy::Tissues::Lymphoid Tissue::Thymus GlandMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction::Wnt Signaling PathwayMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::beta Cateninresearch article32041953open access10.1038/s41467-020-14442-62041-1723PMC7010798