Haematopoiesis articles within Nature Communications

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  • Article
    | Open Access

    Haematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here the authors demonstrate that differentially accessible regions in aged HSC chromatin are enriched for stress-responsive enhancers and act as an epigenetic hub to augment transcriptional responses of aged HSCs to external stimuli.

    • Naoki Itokawa
    • , Motohiko Oshima
    •  & Atsushi Iwama

  • Article
    | Open Access

    The colonization of bone marrow by haematopoietic stem and progenitor cells is critical for lifelong blood cell formation. Here the authors report distinct features of fetal bone marrow and show that artery-derived signals promote haematopoietic colonization.

    • Yang Liu
    • , Qi Chen
    •  & Ralf H. Adams

  • Article
    | Open Access

    RUNX1 is a large and complex gene with two alternative promoters and multiple hematopoietic enhancers. Here the authors show that unlike smaller genes Runx1 becomes sub-compartmentalized during differentiation and gene activation. This subcompartmentalization partially depends on CTCF binding at promoter-proximal CTCF sites and transcription.

    • Dominic D. G. Owens
    • , Giorgio Anselmi
    •  & Marella F. T. R. de Bruijn

  • Article
    | Open Access

    Here, the authors employed Hi-C and low-input itChIP-seq in four rare populations of the hematopoietic stem cell (HSC) ontogeny trajectory across early arterial endothelial cells (eAECs), hemogenic endothelial cells (HECs), pre-HSCs, and long-term HSCs (LT-HSCs) from mouse embryos to show that active histone modifications are largely set up in eAECs and 3D genome is then subsequently configured.

    • Chen C. Li
    • , Guangyu Zhang
    •  & Aibin He

  • Article
    | Open Access

    Lineage differentiation and commitment is driven by transcription regulators and chromatin changes. Here the authors report daily profiling of chromatin accessibility and transcriptome changes during human erythropoiesis, relating these changes to lineage potential between erythropoiesis and megakaryopoieis.

    • Grigorios Georgolopoulos
    • , Nikoletta Psatha
    •  & Jeff Vierstra

  • 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

    Genetic mechanisms underlying fetal hemoglobin (HbF) regulation and switching are not fully understood. Here, the authors develop a single-cell genome editing functional assay to model how effects of mutation-harbouring functional elements contribute to HbF expression.

    • Yong Shen
    • , Jeffrey M. Verboon
    •  & Vijay G. Sankaran

  • Article
    | Open Access

    Reactive oxygen species (ROS) are metabolic by-products which in excess can be toxic for hematopoietic stem and progenitor cells (HSPCs). Here the authors show that toxic ROS are transferred by expanding HSPCs to the zebrafish developmental niche via connexin Cx41.8, where Ifi30 promotes their detoxification.

    • Pietro Cacialli
    • , Christopher B. Mahony
    •  & Julien Y. Bertrand

  • Article
    | Open Access

    Globin loci harbor genes that are expressed embryonically and silenced postnatally. Here the authors show that zeta-globin silencing depends upon selective hypoacetylation of its TAD subdomain, which blocks its interaction with the alpha-globin super-enhancer, and zeta-globin can be reactivated by acetylation.

    • Andrew J. King
    • , Duantida Songdej
    •  & Christian Babbs

  • Article
    | Open Access

    Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.

    • Anne Kathrin Lösslein
    • , Florens Lohrmann
    •  & Philipp Henneke

  • Article
    | Open Access

    Leukaemic stem cells drive acute myeloid leukaemia (AML) progression and relapse but they are incompletely characterized. Here, the authors combine single-cell transcriptomics and clonal tracking using nuclear and mitochondrial somatic variants to distinguish healthy, pre-leukaemic and leukaemic stem cells in AML.

    • Lars Velten
    • , Benjamin A. Story
    •  & Lars M. Steinmetz

  • Article
    | Open Access

    Type 2 conventional dendritic cells (cDC2) are important immune activators in adults, but their development and functions at the neonatal stage remain unclear. Here the authors show, using fate-mapping and single-cell RNA sequencing, that neonatal cDC2 come from multiple origins, but converge functionally as potent immune activators upon proper stimuli.

    • Nikos E. Papaioannou
    • , Natallia Salei
    •  & Barbara U. Schraml

  • 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

    Developing T cells commit to either CD4/helper or CD8/cytotoxic lineage in the thymus, but how CD4 and CD8 coreceptors and TCR signaling dictate this selection process is still unclear. Here the authors use single cell RNA sequencing of mouse thymocytes to show that, in selection intermediates, TCR signaling strength informs coreceptor expression timing.

    • Mohammad M. Karimi
    • , Ya Guo
    •  & Matthias Merkenschlager

  • 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

    Arterial macrophages develop from either yolk sac or bone marrow progenitors. Here, the author show that ageing-induced reduction of arterial macrophages is not replenished by bone marrow-derived cells, but under inflammatory conditions circulating monocytes are recruited to maintain homeostasis, while arterial macrophages of yolk sac origin carry out tissue repair.

    • Tobias Weinberger
    • , Dena Esfandyari
    •  & Christian Schulz

  • Article
    | Open Access

    How the Drosophila lymph gland hemocytes develop and are regulated at a single-cell level is unclear. Here, the authors use single-cell RNA sequencing to show heterogeneity of developing hemocytes in the lymph gland and how they react to wasp infestation, and compare hemocytes from two independent origins.

    • Bumsik Cho
    • , Sang-Ho Yoon
    •  & Jiwon Shim

  • Article
    | Open Access

    The developmental origins and functions of testis macrophages remain incompletely characterized. Here, the authors show, using histology, high-dimensional mass cytometry and cell fate-mapping data, that interstitial and peritubular macrophages originate from distinct precursors and contribute distinctly to spermatogenesis.

    • Emmi Lokka
    • , Laura Lintukorpi
    •  & Marko Salmi

  • 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

    Spinal cord injury (SCI) often leads to immune dysfunction, but mechanistic insights are still lacking. Here the authors show that SCI alters chemokine signaling and induces long, persisting defects in hematopoietic stem and progenitor cell migration, thereby entrapping them in the bone marrow and disrupting peripheral immune homeostasis.

    • Randall S. Carpenter
    • , Jessica M. Marbourg
    •  & Phillip G. Popovich

  • Article
    | Open Access

    The molecular basis of the clinically important MAM blood group antigen present in most humans is unknown. We identify EMP3 as its encoding gene, establishing MAM as a new blood group system, and demonstrate the role of EMP3 in erythropoiesis through its interaction with the signalling molecule CD44.

    • Nicole Thornton
    • , Vanja Karamatic Crew
    •  & David J. Anstee

  • 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

    Renal macrophages (RMs) can be of bone marrow or embryonic origin, but their abundance, fate and metabolic profiles in physiological and pathogenic settings are still unclear. Here the authors show, by characterizing these two RMs in multiple transgenic mouse lines, that they exhibit distinct dynamics, homeostasis, immune activity, and metabolic properties.

    • Fengming Liu
    • , Shen Dai
    •  & Xuebin Qin

  • Article
    | Open Access

    PU.1 is a master TF of hematopoietic lineage differentiation. Here the authors analyse properties of PU.1 DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression, and uncover the mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1.

    • Julia Minderjahn
    • , Andreas Schmidt
    •  & Michael Rehli

  • Article
    | Open Access

    Spondyloarthritis pathology is manifested by increased myeloid infiltration of the joints. Here the authors show that in a mouse model of spondyloarthritis, a single dose of a microbial ligand curdlan induces persistent extramedullary myelopoiesis in the spleen and joints, which is driven by GM-CSF and can be amplified by exogenous IL-33.

    • Daniel Regan-Komito
    • , James W. Swann
    •  & Thibault Griseri

  • 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

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    •  & Jim R. Hughes

  • Article
    | Open Access

    There is limited knowledge of markers to identify various waves of murine embryonic hematopoiesis. Here, the authors show that the expression of toll-like receptor 2 (TLR2) on E7.5 c-kit+ cells marks the emergence of erythro-myeloid progenitor precursors and that the Tlr2 locus is active in E8.5 precursors of adult HSCs.

    • Jana Balounová
    • , Iva Šplíchalová
    •  & Dominik Filipp

  • 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

    Previous gene editing in haematopoietic stem cells (HSCs) has focussed on a heterogeneous CD34+ population. Here, the authors demonstrate high efficiency CRISPR/Cas9-based editing of purified long-term HSCs using non-homologous end joining and homology-directed repair, by directing isoform-specific expression of GATA1.

    • Elvin Wagenblast
    • , Maria Azkanaz
    •  & Eric R. Lechman

  • Article
    | Open Access

    Here, the authors show that reticulocytes derived from immortalized erythroblasts support invasion and development of Plasmodium falciparum and use CRISPR-mediated gene knockout and complementation of an invasion receptor to demonstrate utility of this model system for research in malaria invasion.

    • Timothy J. Satchwell
    • , Katherine E. Wright
    •  & Jake Baum

  • Article
    | Open Access

    HSCs emerge from haemogenic endothelium (HE) in the dorsal aorta but whether these tissues share a common lineage is unclear. Here, the authors use a zebrafish runx1 reporter to show that HE maintains an arterial gene expression profile in the absence of Runx1, suggesting the aortic endothelium as a precursor of HE.

    • Florian Bonkhofer
    • , Rossella Rispoli
    •  & Roger Patient

  • 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

    Influenza viremia is rare in human blood and not well studied. Here, the authors show that influenza can be found in human platelets and that platelet engulfment of influenza A results in TLR7-dependent C3 release, which in turn promotes neutrophil-DNA release and formation of platelet-DNA aggregates.

    • Milka Koupenova
    • , Heather A. Corkrey
    •  & Jane E. Freedman

  • Article
    | Open Access

    In vitro differentiation of red blood cells (RBCs) is a desirable therapy for various disorders. Here the authors develop a culture system using stem cell-derived macrophages to show that inducible expression of a transcription factor, KLF1, enhances RBC production, potentially through the induction of three soluble factors, ANGPTL7, IL33 and SERPINB2.

    • Martha Lopez-Yrigoyen
    • , Cheng-Tao Yang
    •  & Lesley M. Forrester

  • Article
    | Open Access

    Long non-coding RNAs (lncRNA) constitute a large fraction of human transcriptome, and are reported, individually, for context-specific regulatory functions. Here the authors expand our understanding by providing a systemic, unbiased annotation of lncRNA to establish an atlas of lncRNA landscape during the induction of human humoral immune responses.

    • Xabier Agirre
    • , Cem Meydan
    •  & Ari Melnick

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