Lymphopoiesis articles within Nature Communications

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  • Article
    | Open Access

    Self-tolerance is established during B cell development but the contribution of clonal deletion, receptor editing, anergy and apoptosis is debated. Here we show that although apoptosis does occur in a high proportion of transitional B cells after exiting the bone marrow, the reactivity of apoptotic B cells does not differ from that of viable cells, which argues against apoptosis as major mechanism to eliminate self-reactive and polyreactive clones.

    • Mikala JoAnn Simpson
    • , Anna Minh Newen
    •  & Christian Thomas Mayer

  • Article
    | Open Access

    Naked mole-rats are long-lived rodents known to be resistant to the development of cancer, yet their immune system remains poorly explored. Here, the authors identify natural killer-like effector γδ T cells that express a dominant γδ T cell receptor and may serve a role in tumour immunosurveillance.

    • Guillem Sanchez Sanchez
    • , Stephan Emmrich
    •  & David Vermijlen

  • Article
    | Open Access

    The molecular mechanisms that maintain thymic epithelial cell (TEC) identity throughout life are incompletely understood. Here, the authors demonstrate that the transcription factor, Ovol2, maintains post-natal TECs by preventing their epithelial-to-mesenchymal transition.

    • Xue Zhong
    • , Nagesh Peddada
    •  & Bruce Beutler

  • Article
    | Open Access

    Knowledge about the ontogeny of T cells in the thymus relies heavily on mouse studies because of difficulty to obtain human material. Here the authors perform a single cell analysis of thymocytes from human fetal and paediatric thymic samples to characterise the development of human γδ T cells in the thymus.

    • Guillem Sanchez Sanchez
    • , Maria Papadopoulou
    •  & David Vermijlen

  • Article
    | Open Access

    Innate lymphoid cells (ILC) are effector cells that rapidly respond to immune evading stimuli, and despite their functional diversity arise from common precursors. Authors here show how the Notch signalling pathway orchestrates ILC development from circulating human ILC precursors via RORC and its target IL-23R.

    • Carys A. Croft
    • , Anna Thaller
    •  & James P. Di Santo

  • Article
    | Open Access

    Natural Killer cell development is controlled by two related transcription factors, Eomes and T-bet. Authors show here that while the two factors share a large proportion of their target genes, they regulate distinct developmental processes by differing in their pattern of expression and in their associated co-factors.

    • Jiang Zhang
    • , Stéphanie Le Gras
    •  & Thierry Walzer

  • Article
    | Open Access

    T-cell immunotherapies, such as CAR-T immunotherapy, are being developed against a wide variety of diseases. Here the authors report the feeder-free, scalable differentiation of human induced pluripotent cells (iPSCs) to T-cells with T-cell receptor dependent anti-tumour function in vitro and in vivo.

    • Shoichi Iriguchi
    • , Yutaka Yasui
    •  & Shin Kaneko

  • Article
    | Open Access

    Innate-like T cells such as invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells both develop in the thymus. Here the authors use single-cell RNA sequencing to show that mouse iNKT and MAIT share components of developmental regulation, with a transcription factor, Hivep3, implicated for the maturation of both cell types.

    • S. Harsha Krovi
    • , Jingjing Zhang
    •  & Laurent Gapin

  • Article
    | Open Access

    Ageing of the haematopoietic system is accompanied by declining erythropoiesis and lymphopoiesis. Here the authors uncover upregulated IL-6 and TGFβ signalling in aged bone marrow stroma; inhibition of these signals reverses age-related haematopoietic defects, re-balancing haematopoietic stem cell lineage output.

    • Simona Valletta
    • , Alexander Thomas
    •  & Claus Nerlov

  • Article
    | Open Access

    B cell development is tightly regulated in a stepwise manner to ensure proper generation of repertoire diversity via somatic gene rearrangements. Here, the authors show that a transcription factor, Erg, functions at the earliest stage to critically control two downstream factors, Ebf1 and Pax5, for modulating this gene rearrangement process.

    • Ashley P. Ng
    • , Hannah D. Coughlan
    •  & Warren S. Alexander

  • Article
    | Open Access

    TGF-β is thought to be important for group 2 innate lymphoid cell (ILC2) function. Here the authors show that TGF-β drives expression of ST2 specifically in ILC2 progenitors and thereby is also important for the development of ILC2s in the bone marrow.

    • Li Wang
    • , Jun Tang
    •  & WanJun Chen

  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    •  & Avinash Bhandoola

  • Article
    | Open Access

    LncRNA loci potentially contain multiple modes that can exert function, including DNA regulatory elements. Here, the authors generated genetic models in mice to dissect the role of the syntenically conserved lncRNA Firre in the context of hematopoiesis.

    • Jordan P. Lewandowski
    • , James C. Lee
    •  & John L. Rinn

  • Article
    | Open Access

    The repertoire of adaptive immune receptor is generated by V(D)J recombination, somatic rearrangements of V, D and J gene segments, in the respective loci. Here the authors show that the deficiency of Setd2, a histone methyl transfer, impairs V(D)J recombination and induces severe developmental blocks in both T and B lineages.

    • Zhongzhong Ji
    • , Yaru Sheng
    •  & Helen He Zhu

  • Article
    | Open Access

    Programmed cell death regulates early development but how various factors (for example, TRADD, FADD and RIPKs) regulate this is unclear. Here, the authors show that a single allele of Tradd is essential for survival, when both Ripk3 and Ripk1 are knocked out in mice, and RIPK1 protects thymocytes from TNF-induced apoptosis.

    • John P. Dowling
    • , Mohamed Alsabbagh
    •  & Jianke Zhang

  • Article
    | Open Access

    The metabolic regulator protein family, mTOR, regulate natural killer (NK) cell development and function, but the underlying mechanism is unclear. Here, the authors show that Raptor/mTORC1 and Rictor/mTORC2 form a feedback crosstalk network to variegate cytokine and cellular signaling and modulate NK maturation and effector functions.

    • Fangjie Wang
    • , Meng Meng
    •  & Youcai Deng

  • Article
    | Open Access

    c-Kit receptor–Kit ligand complex signaling is known to activate c-Kit and is essential for tissue development. Here, Buono et al. show that membrane-bound KitL signaling induces proliferation via CAML-Akt-CREB pathway activation, establishing a role for bidirectional signaling in tissue expansion.

    • Mario Buono
    • , Marie-Laëtitia Thézénas
    •  & Claus Nerlov

  • Article
    | Open Access

    Human blood cells all develop from haematopoietic stem cells (HSCs), classically thought to be multipotent. Here the authors show, using single-cell RNA-seq and functional assays, that loss of erythroid potential and commitment to the myelo-lymphoid lineage occurs within the purest HSC compartment to date.

    • Serena Belluschi
    • , Emily F. Calderbank
    •  & Elisa Laurenti

  • Article
    | Open Access

    Invariant natural killer T (iNKT) cells can be subsetted by their cytokine profiles, but how they develop in the thymus is unclear. Here the authors show, by analysing mice carrying mutant Zap70 genes, that T cell receptor signaling strength induces epigenetic changes of genes to modulate iNKT lineages.

    • Kathryn D. Tuttle
    • , S. Harsha Krovi
    •  & Laurent Gapin

  • Article
    | Open Access

    Invariant natural killer T (iNKT) cells can be subsetted based on their cytokine productions. Here the authors show, using Zap70 mutant mice, that interferon-γ secreting (IFN-γ) iNKT cells may be induced by hampered T cell receptor signallings to help ameliorate interleukin-17-mediated joint inflammation.

    • Meng Zhao
    • , Mattias N. D. Svensson
    •  & Mitchell Kronenberg

  • Article
    | Open Access

    Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.

    • Ailing Liu
    • , Minhui Chen
    •  & Lisa Borghesi

  • Article
    | Open Access

    The γδ T cell pool includes abundant IL-17-producing cells that protect mucosal surfaces, but the signals that control γδ T cell specification are unclear. Here the authors identify a role for the transcription factor HEB, and antagonistic activity of Id3, in the development of these cells.

    • Tracy S. H. In
    • , Ashton Trotman-Grant
    •  & Michele K. Anderson

  • Article
    | Open Access

    Checkpoint kinase 1 (CHK1) is critical for intrinsic cell cycle control and coordination of cell cycle progression. Here the authors show that CHK1 loss or chemical inhibition impacts on normal B cell development, lymphomagenesis and cancer cell survival.

    • Fabian Schuler
    • , Johannes G. Weiss
    •  & Andreas Villunger

  • Article
    | Open Access

    Haematopoiesis and the generation of lymphoid cell subsets are controlled by delicate genetic programs enforced via epigenetic regulation. Here the authors show that Pcid2 interacts with ZNHIT1, a component of the SRCAP chromatin remodelling complex, to critically modulate the differentiation of multipotent progenitors.

    • Buqing Ye
    • , Benyu Liu
    •  & Zusen Fan

  • Article
    | Open Access

    IL-7R activation drives early B cell development, but the signalling is unclear. Here the authors show PLCγ is involved in IL-7R-induced mTOR activation via a DAG/PKC-dependent pathway, and that double deficiency of the two PLCγ isoforms arrests B cell development at the pre-pro-B stage in mice.

    • Mei Yu
    • , Yuhong Chen
    •  & Demin Wang

  • Article
    | Open Access

    ILC2 and ILC3 are generally thought to require IL-7. Here the authors use IL-7 ko mice and provide side-by-side comparison of ILCs from different tissues to show that IL-7 signalling is not required for intestinal ILC maintenance or function and that IL-15 can compensate for absence of IL-7.

    • Michelle L. Robinette
    • , Jennifer K. Bando
    •  & Marco Colonna

  • Article
    | Open Access

    MEF2C is a transcription factor required for B-cell proliferation. Here the authors show that MEF2C is also needed in B-cell development and recovery from stress by inducing expression of DNA repair factors that prevent double stranded breaks and enable VDJ recombination.

    • Wenyuan Wang
    • , Tonis Org
    •  & Hanna K. A. Mikkola

  • Article
    | Open Access

    Quantum annealing can solve hard optimization problems, but it is limited by computational bottlenecks. Here, the author obtains the scaling of spin-glass bottlenecks with the problem size and explains a crossover to exponential complexity for large sizes.

    • Sergey Knysh

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