Biological models articles within Nature Communications

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  • Article
    | Open Access

    The dynamics of chromatin and transcriptional changes underlying Huntington’s disease remain poorly understood. Here the authors use a Huntington’s mouse model to profile the striatal chromatin landscape, finding that the Huntington’s mutation accelerates age-dependent epigenetic and transcriptional changes, and locally affects 3D chromatin organization.

    • Rafael Alcalá-Vida
    • , Jonathan Seguin
    •  & Karine Merienne

  • Perspective
    | Open Access

    Maria Antfolk and Kim Jensen discuss how to model intestinal epithelial cell function in the dish and how various physiologically important environmental conditions, for example, extracellular matrix, pressure and flow, can be modelled and how this is applicable to clinical work.

    • Maria Antfolk
    •  & Kim B. Jensen

  • Article
    | Open Access

    Extensive scars develop in deep wounds as opposed to superficial wounds but it is unclear why. Here, the authors use live imaging of physiologic wounds and scars formed ex vivo to show that fascia fibroblasts upregulate N-cadherin allowing coordinated cell migration that drives extensive scar formation of deep wounds.

    • Dongsheng Jiang
    • , Simon Christ
    •  & Yuval Rinkevich

  • Comment
    | Open Access

    Decision makers must have sufficient confidence in models if they are to influence their decisions. We propose three screening questions to critically evaluate models with respect to their purpose, organization, and evidence. They enable a more transparent, robust, and secure use of model outputs.

    • Volker Grimm
    • , Alice S. A. Johnston
    •  & P. Thorbek

  • Comment
    | Open Access

    There is an urgent need for drugs, therapies and vaccines to be available to protect the human population against COVID-19. One of the first approaches taken in the COVID-19 global response was to consider repurposing licensed drugs. This commentary highlights an extraordinary international collaborative effort of independent researchers who have recently all come to the same conclusion—that chloroquine or hydroxchloroquine are unlikely to provide clinical benefit against COVID-19.

    • S. G. P. Funnell
    • , W. E. Dowling
    •  & C. M. Coleman

  • Article
    | Open Access

    The mechanisms regulating stem cells to give rise to human interfollicular epidermis are unclear. Here, the authors use single cell RNA sequencing to identify heterogeneity within the human neonatal interfollicular epidermis and distinct spatial positioning of at least four basal stem cell populations.

    • Shuxiong Wang
    • , Michael L. Drummond
    •  & Scott X. Atwood

  • Article
    | Open Access

    The ability to culture live pancreatic tissue slices for long periods of time would enable longitudinal studies ex vivo. Here the authors culture human and mouse pancreatic slices in a perfluorocarbon-based culture system and show stable endocrine and exocrine function for up to ten days in culture.

    • Mirza Muhammad Fahd Qadir
    • , Silvia Álvarez-Cubela
    •  & Juan Domínguez-Bendala

  • Article
    | Open Access

    Previous versions of photoactivatable Cre recombinase (PA-Cre) suffered from unintentional recombination in dark conditions. Here, the authors develop an improved version of PA-Cre, called PA-Cre 3.0, which shows reduced leakiness and improved efficiency upon activation, and make mouse lines that express PA-Cre 3.0 conditionally.

    • Kumi Morikawa
    • , Kazuhiro Furuhashi
    •  & Masayuki Yazawa

  • Article
    | Open Access

    The development of post-chemotherapy resistance is a significant issue in the management of AML. Here, Caiado et al. suggest that the issue might be circumvented via upfront combination with hypomethylating agents that shape the clonal dynamics and transcriptional landscape of relapsing AML

    • Francisco Caiado
    • , Diogo Maia-Silva
    •  & Bruno Silva-Santos

  • Article
    | Open Access

    During wound induced hair follicle neogenesis (WIHN), stem cells regenerate hair follicles but how this arises is unclear. Here, the authors show that self-noncoding dsRNA activates the antiviral receptor TLR3 to induce intrinsic retinoic acid, which stimulates WIHN in mice, and in isolated human keratinocyte cells.

    • Dongwon Kim
    • , Ruosi Chen
    •  & Luis A. Garza

  • Article
    | Open Access

    Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism.

    • Martina Theresa Hackl
    • , Clemens Fürnsinn
    •  & Thomas Scherer

  • Article
    | Open Access

    Cultured adult cardiac tissue undergoes rapid dedifferentiation, which hinders chronic in vitro studies. Here the authors investigate biomimetic electromechanical stimulation of adult myocardial slices applying different preload conditions, identifying the optimum sarcomere length for prolonged culturing, and investigating transcriptional profiles associated with functional preservation.

    • Samuel A. Watson
    • , James Duff
    •  & Cesare M. Terracciano

  • Article
    | Open Access

    The transcriptional regulator YAP is regarded as the universal mechanotransducer, largely from 2D culture studies. Here the authors show that in breast cancer patient tissues and cells in 3D culture, mechanical signals are transduced independently of YAP, questioning YAP as a therapeutic target.

    • Joanna Y. Lee
    • , Jessica K. Chang
    •  & Ovijit Chaudhuri

  • Article
    | Open Access

    Imaging the mouse brain using glass cranial windows has limitations in terms of flexibility and long-term imaging. Here the authors engineer transparent polymer skulls that can fit various skull morphologies and can be implanted for over 300 days, enabling simultaneous high resolution brain imaging and electrophysiology across large cortical areas.

    • Leila Ghanbari
    • , Russell E. Carter
    •  & Suhasa B. Kodandaramaiah

  • Article
    | Open Access

    Oral vaccination is a potential option to elicit systemic and mucosal immunity against HIV. Here, Jones et al. show that oral vaccination with a modified needle-free injector induces protective immunity against SHIV in non-human primates and is superior to topical application of vaccines to oral tissues.

    • Andrew T. Jones
    • , Xiaoying Shen
    •  & Rama Rao Amara

  • Article
    | Open Access

    Myocardial tissue undergoes steady functional decline when cultured in vitro. Here, the authors report a protocol for culture of human cardiac slices that allows maintenance of contractility for up to four months, and show that the model is suitable for evaluation of drug safety, as exemplified for drugs interfering with cardiomyocyte repolarization.

    • Carola Fischer
    • , Hendrik Milting
    •  & Andreas Dendorfer

  • Article
    | Open Access

    The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4+ T cells is seeded within the first 2 days after infection.

    • James B. Whitney
    • , So-Yon Lim
    •  & Dan H. Barouch

  • Article
    | Open Access

    Human skin constructs hold potential for regenerative medicine, but the incorporation of hair follicles into such constructs is a challenge. Here, the authors use 3D printed molds to pattern hair follicle cell types in a physiological organization, and achieve human hair growth on the back of a mouse.

    • Hasan Erbil Abaci
    • , Abigail Coffman
    •  & Angela M. Christiano

  • Article
    | Open Access

    Individuals with Down Syndrome have hematopoietic abnormalities including high risk of leukaemia. Here the authors show that transcriptional silencing of one chromosome 21 by XIST effectively corrects cell function and development to prevent excessive production of megakaryocytes and erythroids, shown during hematopoietic differentiation of human iPSCs in culture.

    • Jen-Chieh Chiang
    • , Jun Jiang
    •  & Jeanne B. Lawrence

  • Article
    | Open Access

    Allogeneic hematopoietic cell transplantation (allo-HCT) has led to the cure of HIV in one individual, but the underlying mechanisms are unclear. Here, the authors present a model of allo-HCT in SHIV-infected nonhuman primates and show that the SHIV reservoir persists in multiple tissues early after transplantation.

    • Lucrezia Colonna
    • , Christopher W. Peterson
    •  & Leslie S. Kean

  • Article
    | Open Access

    Excessive production of reactive oxygen species (ROS) is associated with cardiac dysfunction, but the causal role of ROS remains poorly understood. Here the authors use an in vivo chemogenetic approach to develop a heart failure model in which generation of hydrogen peroxide in the heart leads to systolic heart failure without fibrotic remodeling.

    • Benjamin Steinhorn
    • , Andrea Sorrentino
    •  & Thomas Michel

  • Article
    | Open Access

    RSV infection is a major cause of bronchiolitis in infants and maternal vaccination is a potential preventive option. Here, Blanco et al. show efficacy of a Newcastle disease virus-based virus-like particle vaccine candidate in naive and pre-exposed cotton rat dams and their offspring.

    • Jorge C. G. Blanco
    • , Lioubov M. Pletneva
    •  & Trudy G. Morrison

  • Article
    | Open Access

    The integrity of the stratified epithelia relies on controlled cell turnover but it is unclear how mRNA binding proteins regulates this. Here, the authors show that the RNA binding protein Y-box binding protein-1 translationally represses cytokines, so preventing senescence and maintaining epidermal homeostasis.

    • Eunjeong Kwon
    • , Kristina Todorova
    •  & Anna Mandinova

  • Article
    | Open Access

    G protein-coupled receptors are involved in numerous physiological functions, thus, they represent potential pharmaceutical targets. Here Kono et al. describe a new mouse model to image GPCR activation in real-time by exploiting firefly split luciferase fragment complementation that can be detected by bioluminescence imaging.

    • Mari Kono
    • , Elizabeth G. Conlon
    •  & Richard L. Proia

  • Article
    | Open Access

    Early in human embryonic development, it is unclear how amniotic sac formation is regulated. Here, the authors use a human pluripotent stem cell-based model, termed the post-implantation amniotic sac embryoid, to recapitulate early embryogenic events of human amniotic sac development.

    • Yue Shao
    • , Kenichiro Taniguchi
    •  & Jianping Fu

  • Article
    | Open Access

    Human liver chimeric mice are increasingly used for drug testing in preclinical development, but express residual murine p450 cytochromes. Here the authors generate mice lacking the Por gene in the liver, and show that human cytochrome metabolism is used following repopulation with human hepatocytes.

    • Mercedes Barzi
    • , Francis P. Pankowicz
    •  & Karl-Dimiter Bissig

  • Article
    | Open Access

    Laboratory mice are the cornerstone of immunology but how well they represent wild mice is not clear. Here the authors compare and contrast various immune parameters between wild-caught mice and laboratory (C57BL/6) mice and identify a previously unknown myeloid cell population specific to wild mice.

    • Stephen Abolins
    • , Elizabeth C. King
    •  & Eleanor M. Riley

  • Article
    | Open Access

    Loss-of-function mutations inPNPLA1, a gene encoding an enzyme with unknown function, cause dry and scaling skin in humans. Using mouse models with PNPLA1 deficiency, the authors show that PNPLA1 participates in the biosynthesis of acylceramide, a lipid component essential for skin barrier function.

    • Tetsuya Hirabayashi
    • , Tatsuki Anjo
    •  & Makoto Murakami

  • Article
    | Open Access

    Nrf2 regulates oxidative and electrophilic stress responses by modulating the expression of enzymes involved in detoxification pathways. Here Suzukiet al. show that Nrf2 activation in early tubular development promotes nephrogenic diabetes insipidus by regulating aquaporin 2 expression and trafficking and water permeability.

    • Takafumi Suzuki
    • , Shiori Seki
    •  & Masayuki Yamamoto

  • Article
    | Open Access

    Three-dimensional culture systems and organoids for mammary glands are important to understand mammary gland development. Here, the authors identify conditions (including Neuregulin 1 and R-spondin 1) that allow the culture of organoids that are responsive to hormonal stimulation for up to 2.5 months.

    • Thierry Jardé
    • , Bethan Lloyd-Lewis
    •  & Trevor C. Dale

  • Article
    | Open Access

    The genome of some bacteria consists of two or more chromosomes or replicons. Here, diCenzo et al. integrate genome-scale metabolic modelling and growth data from a collection of mutants of the plant symbiont Sinorhizobium melilotito estimate the fitness contribution of each replicon in three environments.

    • George C. diCenzo
    • , Alice Checcucci
    •  & Marco Fondi

  • Article
    | Open Access

    Animal models of infection with Zika virus (ZIKV) are urgently needed for a better understanding of pathogenesis and for testing potential therapies. Here, the authors describe infection of rhesus macaques with an Asian-lineage ZIKV strain as a relevant animal model for studying ZIKV pathogenesis.

    • Dawn M. Dudley
    • , Matthew T. Aliota
    •  & David H. O’Connor

  • Article
    | Open Access

    Imaging tools for evaluating progression of Alzheimer’s disease have been lacking. Here the authors develop a blood brain barrier-permeable Aß probe based on a radiolabelled, anti-Aß antibody, and report age-dependent brain uptake visualized in vivo with PET in mouse models of the disease.

    • Dag Sehlin
    • , Xiaotian T. Fang
    •  & Stina Syvänen

  • Article
    | Open Access

    The domestic dog is an important model organism for our understanding of cancer and other diseases. Here the authors conduct a genome-wide association study across multiple breeds and identify novel loci significantly associated with several complex diseases and morphological traits.

    • Jessica J. Hayward
    • , Marta G. Castelhano
    •  & Adam R. Boyko

  • Article
    | Open Access

    Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al. show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.

    • Ronald A. Albright
    • , Paul Stabach
    •  & Demetrios T. Braddock

  • Article
    | Open Access

    Mice engrafted with human cells are useful models for research on human malaria parasites. Here the authors show that the complete life cycle of Plasmodium falciparum and the liver stages of Plasmodium ovalecan be studied in mice doubly engrafted with human primary hepatocytes and red blood cells.

    • Valérie Soulard
    • , Henriette Bosson-Vanga
    •  & Dominique Mazier

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