Anatomy

  • Article
    | Open Access

    Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying mesenchymal subtypes and undescribed endocrine progenitors.

    • Lauren E. Byrnes
    • , Daniel M. Wong
    •  & Julie B. Sneddon
  • Article
    | Open Access

    The role of the gut microbiota in hepatic lipid metabolism is controversial and incompletely understood. Here the authors perform multi-omics analyses of altered lipid metabolic processes in germ-free and specific pathogen-free mice, revealing how the gut microbiota affects hepatic fatty acid desaturation and elongation.

    • Alida Kindt
    • , Gerhard Liebisch
    •  & Josef Ecker
  • Article
    | Open Access

    Fibro-adipogenic progenitors (FAPs) resident in skeletal muscle are involved in both regeneration and maladaptive processes. Here, the authors identify subpopulations of FAPs with biological activities implicated in physiological muscle repair that are altered in pathological conditions such as muscular dystrophies.

    • Barbora Malecova
    • , Sole Gatto
    •  & Pier Lorenzo Puri
  • Article
    | Open Access

    Muscular dystrophies are characterised by extensive myofibre cell death. Here Morgan et al. show that RIPK3-mediated necroptosis contributes to myofibre cell death in Duchenne muscular dystrophy, and that RIPK3 deletion protects dystrophic mice against myofibre degeneration.

    • Jennifer E. Morgan
    • , Alexandre Prola
    •  & Maximilien Bencze
  • Article
    | Open Access

    Endurance and resistance exercise have different effects on skeletal muscle phenotype. Using mouse models and human subjects, the authors show that JNK/Smad2 signaling acts as molecular switch that when activated by resistance exercise leads to hypertrophy, and when inhibited promotes endurance adaptations in muscle.

    • Sarah J. Lessard
    • , Tara L. MacDonald
    •  & Laurie J. Goodyear
  • Article
    | Open Access

    Zika virus (ZIKV) can persist for months in semen and sperm. Here, the authors show that germ cells, compared to other cell types in the reproductive tract, are most susceptible to ZIKV and produce high levels of progeny virus, which coincides with decreased expression of the interferon-stimulated gene Ifi44l.

    • Christopher L. Robinson
    • , Angie C. N. Chong
    •  & Shuibing Chen
  • Article
    | Open Access

    Hyperinsulinemia can precede the development of insulin resistance. Here the authors identify a PKD2 mutation that leads to hyperinsulinemia and insulin resistance in Rhesus monkey and show that PKD2 deficiency promotes beta cell insulin secretion by activating L-type Ca2+ channels.

    • Yao Xiao
    • , Can Wang
    •  & Xiuqin Zhang
  • Article
    | Open Access

    Insulin secretion by β-cells is stimulated by glucose and is dependent on the induction of β-cell membrane depolarization, mainly driven by the closure of KATP channels, which in turn promotes voltage-gated Ca2+ channel opening. Here the authors show that LRRC8 volume-regulated anion channels (VRACs) modulate glucose-stimulated calcium increase and insulin secretion.

    • Till Stuhlmann
    • , Rosa Planells-Cases
    •  & Thomas J. Jentsch
  • Article
    | Open Access

    CD4+ T cells are critical for the development of lymphedema. Here the authors show how these cells contribute to lymphedema and identify that the sphingosine-1-phosphate receptor modulator FTY720 can prevent lymphedema in a mouse tail injury model by blocking the release of CD4+ T cells from the lymph nodes to the skin.

    • Gabriela D. García Nores
    • , Catherine L. Ly
    •  & Babak J. Mehrara
  • Article
    | Open Access

    Mechanical forces exerted on tendons during locomotion cannot be readily measured without invasive methods. Here, the authors develop a non-invasive wearable device to track tendon loads by measuring shear wave propagation speed, and demonstrate its use during dynamic human movements.

    • Jack A. Martin
    • , Scott C. E. Brandon
    •  & Darryl G. Thelen
  • Article
    | Open Access

    Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

    • Joachim Pircher
    • , Thomas Czermak
    •  & Christian Schulz
  • Article
    | Open Access

    Type 1 diabetes mellitus (T1DM) is characterized by beta cell loss because of an autoimmune attack. Here the authors show that an agonist for LRH-1/NR5A2, a nuclear receptor known to be protective against beta cell apoptosis, inhibits immune-mediated inflammation and hyperglycemia in T1DM mouse models.

    • Nadia Cobo-Vuilleumier
    • , Petra I. Lorenzo
    •  & Benoit R. Gauthier
  • Article
    | Open Access

    The authors have previously shown that membrane voltage can influence embryonic patterning during development. Here, the authors computationally model how nicotine disrupts Xenopus embryogenesis by perturbing voltage gradients, and rescue nicotine-inducted defects with HCN2 channel expression.

    • Vaibhav P. Pai
    • , Alexis Pietak
    •  & Michael Levin
  • Article
    | Open Access

    Heterotopic ossification (HO) is a painful disease of unknown etiology characterized by extraskeletal bone formation after injury. Here the authors show that TGF-β is increased in HO lesions, where it promotes the early stages of HO pathology, and demonstrate that TGF-β inhibition ameliorates HO in mice.

    • Xiao Wang
    • , Fengfeng Li
    •  & Xu Cao
  • Article
    | Open Access

    Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of KATP channels in α-cells.

    • Davide Basco
    • , Quan Zhang
    •  & Bernard Thorens
  • Article
    | Open Access

    Fibrodysplasia ossificans progressiva is a severe disorder characterized by heterotopic ossification, and is caused by mutations in ACVR1. Here, the authors show that expression of mutant ACVR1 in fibro/adipogenic progenitors recapitulates disease progression, and that this can be halted by systemic inhibition of activin A in mice.

    • John B. Lees-Shepard
    • , Masakazu Yamamoto
    •  & David J. Goldhamer
  • Article
    | Open Access

    Adult beta cells, which are highly specialised insulin-secreting cells, rarely replicate. Puri et al. demonstrate that beta cell proliferative capacity is inversely correlated with their functionality and differentiation state, by inducing proliferation of adult cells with ectopic overexpression of the cell cycle regulator c-Myc.

    • Sapna Puri
    • , Nilotpal Roy
    •  & Matthias Hebrok
  • Article
    | Open Access

    Satellite cells can differentiate both into myocytes and brown adipocytes. Here, the authors show that the histone demethylase Lsd1 prevents adipogenic differentiation of satellite cells by repressing expression of Glis1, and that its ablation changes satellite cell fate towards brown adipocytes and delays muscle regeneration in mice.

    • Milica Tosic
    • , Anita Allen
    •  & Roland Schüle
  • Article
    | Open Access

    Communication between osteoblasts and osteoclasts is essential for bone homeostasis, but the mode of interaction is unclear. The authors use intravital two-photon microscopy in mice to show that these cells directly interact, regulating activity of osteoclasts, and that the interaction is modulated by parathyroid hormone administration.

    • Masayuki Furuya
    • , Junichi Kikuta
    •  & Masaru Ishii
  • Article
    | Open Access

    The generation of functional skeletal muscle tissue from human pluripotent stem cells has not been reported. Here, the authors describe engineering of contractile skeletal muscle bundles in culture, which become vascularized and maintain functionality when transplanted into mice.

    • Lingjun Rao
    • , Ying Qian
    •  & Nenad Bursac
  • Article
    | Open Access

    Short-chain fatty acids (SCFA) are a main class of metabolites derived from fermentation of dietary fibre in the intestine. Here, the authors show that dietary administration of SCFA is associated with inhibition of osteoclast differentiation, increased bone mass, and reduced pathological bone loss in mice.

    • Sébastien Lucas
    • , Yasunori Omata
    •  & Mario M. Zaiss
  • Article
    | Open Access

    Facioscapulohumeral muscular dystrophy is a myopathy linked to ectopic expression of the DUX4 transcription factor. The authors show that the suppression of targets genes of the myogenesis regulator PAX7 is a signature of FSHD, and might explain oxidative stress sensitivity and epigenetic changes.

    • Christopher R. S. Banerji
    • , Maryna Panamarova
    •  & Peter S. Zammit
  • Article
    | Open Access

    Drugs targeting myostatin reverse muscle wasting in animal models, but have limited efficacy in patients. The authors show that the myostatin pathway is downregulated in patients, possibly explaining the poor outcome of anti-myostatin approaches, and that it can be reactivated by correcting disease-causing mutations in mice.

    • Virginie Mariot
    • , Romain Joubert
    •  & Julie Dumonceaux
  • Article
    | Open Access

    Myoblast fusion is essential for skeletal muscle development and regeneration. Here the authors show that MyD88 is upregulated during myogenesis and during muscle growth, signals via the NF-κB and Wnt pathways, and that its expression modulates myoblast fusion and myofiber size in mice.

    • Sajedah M. Hindi
    • , Jonghyun Shin
    •  & Ashok Kumar
  • Article
    | Open Access

    Osteoclasts are involved in arthritis, and their differentiation depends on RANKL signaling. The author show that the ROS-scavenging protein DJ-1 negatively regulates RANKL signaling and that its ablation increases osteoclast numbers and exacerbates bone damage in mouse models of arthritis.

    • Hyuk Soon Kim
    • , Seung Taek Nam
    •  & Wahn Soo Choi
  • Article
    | Open Access

    Mesenchymal stem cells are essential for bone development, but it is unclear if their activity is maintained after late puberty, when bone growth decelerates. The authors show that during late puberty in mice, these cells undergo senescence under the epigenetic control of Ezh2.

    • Changjun Li
    • , Yu Chai
    •  & Mei Wan
  • Article
    | Open Access

    The mechanisms underlying tissue fibrosis are unclear. The authors show that mesenchymal cells expressing PDGFRβ mediate fibrosis in skeletal muscle and heart via a mechanism involving αv integrin, and that inhibitors of αv integrins attenuate fibrotic responses in mice.

    • I. R. Murray
    • , Z. N. Gonzalez
    •  & N. C. Henderson
  • Article
    | Open Access

    Strategies aimed at promoting muscle regeneration to treat muscular dystrophy have met with limited success. Here the authors show instead that delaying muscle regeneration, by ablation of the transcription factor Nfix, ameliorates muscular dystrophy in mice.

    • Giuliana Rossi
    • , Chiara Bonfanti
    •  & Graziella Messina
  • Article
    | Open Access

    Exon skipping is a strategy for the treatment of Duchenne muscular dystrophy, but has variable efficacy. Here, the authors show that dystrophin restoration occurs preferentially in areas of myofiber regeneration, where antisense oligonucleotides are stored in macrophages and delivered to myoblasts and newly formed myotubes

    • James S. Novak
    • , Marshall W. Hogarth
    •  & Terence A. Partridge
  • Article
    | Open Access

    Satellite cells are crucial for growth and regeneration of skeletal muscle. Here the authors show that in response to muscle injury, macrophages secrete Adamts1, which induces satellite cell activation by modulating Notch1 signaling.

    • Hongqing Du
    • , Chung-Hsuan Shih
    •  & Brian J. Feldman
  • Article
    | Open Access

    Cholinergic neurons innervate multiple layers in the main olfactory bulb but the precise circuitry of this input is not known. Here the authors show that VGLUT3+ cholinergic neurons selectively innervate deep short axon cells in specific layers and elicit robust monosynaptic GABAergic and nicotinic postsynaptic currents.

    • Daniel T. Case
    • , Shawn D. Burton
    •  & Rebecca P. Seal
  • Article
    | Open Access

    Facioscapulohumeral muscular dystrophy is a severe myopathy that is caused by abnormal activation of DUX4, and for which a suitable mouse model does not exist. Here, the authors generate a novel mouse model with titratable expression of DUX4, and show that it recapitulates several features of the human pathology.

    • Darko Bosnakovski
    • , Sunny S. K. Chan
    •  & Michael Kyba
  • Article
    | Open Access

    In mammalian skeletal muscle, the DHPR functions as a voltage sensor to trigger muscle contraction and as a Ca2+ channel. Here the authors show that mice where Ca2+ influx through the DHPR is eliminated display no difference in skeletal muscle function, suggesting that the Ca2+ influx through this channel is vestigial.

    • Anamika Dayal
    • , Kai Schrötter
    •  & Manfred Grabner
  • Article
    | Open Access

    Our incomplete understanding of how pancreatic beta cells form limits the generation of beta-like cells from human pluripotent stem cells (hPSC). Here, the authors identify a ROCKII inhibitor H1152 as increasing insulin secreting cells from hPSCs and improving beta-cell maturation on transplantation in vivo.

    • Zaniar Ghazizadeh
    • , Der-I Kao
    •  & Shuibing Chen
  • Article
    | Open Access

    Adipose tissue contains macrophages that can influence both local and systemic metabolism via the secretion of cytokines. Here, Nawaz et al. report that M2-like macrophages, present in adipose tissue, create a microenvironment that inhibits proliferation of adipocyte progenitors due to the secretion of TGF-β1

    • Allah Nawaz
    • , Aminuddin Aminuddin
    •  & Kazuyuki Tobe
  • Article
    | Open Access

    Duchenne muscular dystrophy is a progressive degenerative disease of muscles caused by mutations in the dystrophin gene. Here the authors use AAV vectors to deliver microdystrophin to dogs with muscular dystrophy, and show restoration of dystrophin expression and reduction of symptoms up to 26 months of age.

    • Caroline Le Guiner
    • , Laurent Servais
    •  & George Dickson
  • Article
    | Open Access

    Deregulation of mTORC1 pathway has been associated with several human diseases including diabetes, neurodegeneration and cancer. Here Blandino-Rosanoet al. show that mTORC1 signalling controls insulin secretion and β-cell maintenance by regulation of β-cell proliferation, apoptosis and autophagy and insulin processing.

    • Manuel Blandino-Rosano
    • , Rebecca Barbaresso
    •  & Ernesto Bernal-Mizrachi
  • 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