Anatomy

  • Article
    | Open Access

    Nebulin-based nemaline myopathy is a heterogenous disease with unclear pathological mechanisms. Here, the authors generate a mouse model that mimics the most common genetic cause of the disease and demonstrate that muscle weakness in this model is associated with twisted actin filaments and altered tropomyosin and troponin behaviour.

    • Johan Lindqvist
    • , Weikang Ma
    • , Frank Li
    • , Yaeren Hernandez
    • , Justin Kolb
    • , Balazs Kiss
    • , Paola Tonino
    • , Robbert van der Pijl
    • , Esmat Karimi
    • , Henry Gong
    • , Josh Strom
    • , Zaynab Hourani
    • , John E. Smith III
    • , Coen Ottenheijm
    • , Thomas Irving
    •  & Henk Granzier
  • Article
    | Open Access

    Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

    • Quinn P. Peterson
    • , Adrian Veres
    • , Lihua Chen
    • , Michael Q. Slama
    • , Jennifer H. R. Kenty
    • , Shaimaa Hassoun
    • , Matthew R. Brown
    • , Haiqiang Dou
    • , Caden D. Duffy
    • , Quan Zhou
    • , Aleksey V. Matveyenko
    • , Björn Tyrberg
    • , Maria Sörhede-Winzell
    • , Patrik Rorsman
    •  & Douglas A. Melton
  • Article
    | Open Access

    The origin of the heterogeneity of metabolic and inflammatory profiles exhibited by white adipocytes is little understood. Here, using scRNA-seq and computational methods, the authors show that differentiating preadipocytes exhibit gene expression differences and suggest underlying regulators.

    • Alfred K. Ramirez
    • , Simon N. Dankel
    • , Bashir Rastegarpanah
    • , Weikang Cai
    • , Ruidan Xue
    • , Mark Crovella
    • , Yu-Hua Tseng
    • , C. Ronald Kahn
    •  & Simon Kasif
  • Article
    | Open Access

    Glucose metabolism is regulated by hypothalamic brain functions and factors produced by peripheral tissues. Here, the authors show that the regulator of food intake Brain-derived neurotrophic factor is also produced and secreted by muscle and stimulates pancreas insulin release.

    • Gianluca Fulgenzi
    • , Zhenyi Hong
    • , Francesco Tomassoni-Ardori
    • , Luiz F. Barella
    • , Jodi Becker
    • , Colleen Barrick
    • , Deborah Swing
    • , Sudhirkumar Yanpallewar
    • , Brad St Croix
    • , Jürgen Wess
    • , Oksana Gavrilova
    •  & Lino Tessarollo
  • Article
    | Open Access

    Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

    • Farnaz Shamsi
    • , Ruidan Xue
    • , Tian Lian Huang
    • , Morten Lundh
    • , Yang Liu
    • , Luiz O. Leiria
    • , Matthew D. Lynes
    • , Elena Kempf
    • , Chih-Hao Wang
    • , Satoru Sugimoto
    • , Pasquale Nigro
    • , Kathrin Landgraf
    • , Tim Schulz
    • , Yiming Li
    • , Brice Emanuelli
    • , Srinivas Kothakota
    • , Lewis T. Williams
    • , Niels Jessen
    • , Steen Bønløkke Pedersen
    • , Yvonne Böttcher
    • , Matthias Blüher
    • , Antje Körner
    • , Laurie J. Goodyear
    • , Moosa Mohammadi
    • , C. Ronald Kahn
    •  & Yu-Hua Tseng
  • Article
    | Open Access

    Denervation of muscle fibres induces muscle atrophy, via mechanisms that remain unclear. Here, the authors show that binding of acetylcoline to its receptor at the neuromuscular junction represses the expression of connexins 43 and 45, which promote atrophy, and is sufficient to prevent denervation-induced loss of myofibre mass.

    • Bruno A. Cisterna
    • , Aníbal A. Vargas
    • , Carlos Puebla
    • , Paola Fernández
    • , Rosalba Escamilla
    • , Carlos F. Lagos
    • , María F. Matus
    • , Cristian Vilos
    • , Luis A. Cea
    • , Esteban Barnafi
    • , Hugo Gaete
    • , Daniel F. Escobar
    • , Christopher P. Cardozo
    •  & Juan C. Sáez
  • Article
    | Open Access

    An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

    • Rong Fu
    • , Wen-Cong Lv
    • , Ying Xu
    • , Mu-Yun Gong
    • , Xiao-Jie Chen
    • , Nan Jiang
    • , Yan Xu
    • , Qing-Qiang Yao
    • , Lei Di
    • , Tao Lu
    • , Li-Ming Wang
    • , Ran Mo
    •  & Zhao-Qiu Wu
  • Article
    | Open Access

    Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.

    • Julia S. Brunner
    • , Loan Vulliard
    • , Melanie Hofmann
    • , Markus Kieler
    • , Alexander Lercher
    • , Andrea Vogel
    • , Marion Russier
    • , Johanna B. Brüggenthies
    • , Martina Kerndl
    • , Victoria Saferding
    • , Birgit Niederreiter
    • , Alexandra Junza
    • , Annika Frauenstein
    • , Carina Scholtysek
    • , Yohei Mikami
    • , Kristaps Klavins
    • , Gerhard Krönke
    • , Andreas Bergthaler
    • , John J. O’Shea
    • , Thomas Weichhart
    • , Felix Meissner
    • , Josef S. Smolen
    • , Paul Cheng
    • , Oscar Yanes
    • , Jörg Menche
    • , Peter J. Murray
    • , Omar Sharif
    • , Stephan Blüml
    •  & Gernot Schabbauer
  • Article
    | Open Access

    Ageing is associated with muscle atrophy, which negatively impacts quality of life. Here the authors show that expression of sestrins decreases during inactivity and that their overexpression prevents atrophy in mice via modulation of autophagy and protein degradation.

    • Jessica Segalés
    • , Eusebio Perdiguero
    • , Antonio L. Serrano
    • , Pedro Sousa-Victor
    • , Laura Ortet
    • , Mercè Jardí
    • , Andrei V. Budanov
    • , Laura Garcia-Prat
    • , Marco Sandri
    • , David M. Thomson
    • , Michael Karin
    • , Jun Hee Lee
    •  & Pura Muñoz-Cánoves
  • Article
    | Open Access

    Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.

    • Eugenia Migliavacca
    • , Stacey K. H. Tay
    • , Harnish P. Patel
    • , Tanja Sonntag
    • , Gabriele Civiletto
    • , Craig McFarlane
    • , Terence Forrester
    • , Sheila J. Barton
    • , Melvin K. Leow
    • , Elie Antoun
    • , Aline Charpagne
    • , Yap Seng Chong
    • , Patrick Descombes
    • , Lei Feng
    • , Patrice Francis-Emmanuel
    • , Emma S. Garratt
    • , Maria Pilar Giner
    • , Curtis O. Green
    • , Sonia Karaz
    • , Narasimhan Kothandaraman
    • , Julien Marquis
    • , Sylviane Metairon
    • , Sofia Moco
    • , Gail Nelson
    • , Sherry Ngo
    • , Tony Pleasants
    • , Frederic Raymond
    • , Avan A. Sayer
    • , Chu Ming Sim
    • , Jo Slater-Jefferies
    • , Holly E. Syddall
    • , Pei Fang Tan
    • , Philip Titcombe
    • , Candida Vaz
    • , Leo D. Westbury
    • , Gerard Wong
    • , Wu Yonghui
    • , Cyrus Cooper
    • , Allan Sheppard
    • , Keith M. Godfrey
    • , Karen A. Lillycrop
    • , Neerja Karnani
    •  & Jerome N. Feige
  • Article
    | Open Access

    Skeletal muscle stem cells express the transcription factor Pax7. Here, the authors isolate, from human muscle, cells that are positive for the endothelial marker CLEC14A and show that despite not expressing pax7, these cells regenerate muscle and contribute to the muscle stem cell niche when transplanted into mice.

    • Andreas Marg
    • , Helena Escobar
    • , Nikos Karaiskos
    • , Stefanie A. Grunwald
    • , Eric Metzler
    • , Janine Kieshauer
    • , Sascha Sauer
    • , Diana Pasemann
    • , Edoardo Malfatti
    • , Dominique Mompoint
    • , Susanna Quijano-Roy
    • , Anastasiya Boltengagen
    • , Joanna Schneider
    • , Markus Schülke
    • , Séverine Kunz
    • , Robert Carlier
    • , Carmen Birchmeier
    • , Helge Amthor
    • , Andreas Spuler
    • , Christine Kocks
    • , Nikolaus Rajewsky
    •  & Simone Spuler
  • Article
    | Open Access

    The visual word form area (VWFA) is a brain region associated with written language, but it has also been linked to visuospatial attention. Here, the authors reveal distinct structural and functional circuits linking VWFA with language and attention networks, and demonstrate that these circuits separately predict language and attention abilities.

    • Lang Chen
    • , Demian Wassermann
    • , Daniel A. Abrams
    • , John Kochalka
    • , Guillermo Gallardo-Diez
    •  & Vinod Menon
  • Article
    | Open Access

    During high-intensity exercise, muscles convert glucose to lactate, in a process that is energetically less efficient than respiration. Here the authors develop a computational model based on muscle proteomic data showing that bypassing mitochondrial complex I increases ATP production rates, and validate these model predictions in an exercise test on 5 subjects.

    • Avlant Nilsson
    • , Elias Björnson
    • , Mikael Flockhart
    • , Filip J. Larsen
    •  & Jens Nielsen
  • Article
    | Open Access

    Reactive oxygen species (ROS) stimulate GLUT4-mediated glucose transport following contraction of isolated muscle, but it is not clear if this occurs in vivo. Here, the authors show in human volunteers that exercise induces ROS increase in muscle and, using loss of-function animal models, they demonstrate that NOX2 is a major ROS source required to stimulate glucose uptake during exercise.

    • Carlos Henríquez-Olguin
    • , Jonas R. Knudsen
    • , Steffen H. Raun
    • , Zhencheng Li
    • , Emilie Dalbram
    • , Jonas T. Treebak
    • , Lykke Sylow
    • , Rikard Holmdahl
    • , Erik A. Richter
    • , Enrique Jaimovich
    •  & Thomas E. Jensen
  • Article
    | Open Access

    Leflunomide is used for the treatment of rheumatoid arthritis. Here, the authors show that effectiveness is limited in patients with higher levels of serum c-reactive protein (CRP). Using animal models, they show that higher CRP induces HIF1a expression, which in turn interferes with Leflunomide signalling, and that effectiveness of the drug is restored when HIF1a is pharmacologically inhibited.

    • Chao Liang
    • , Jie Li
    • , Cheng Lu
    • , Duoli Xie
    • , Jin Liu
    • , Chuanxin Zhong
    • , Xiaohao Wu
    • , Rongchen Dai
    • , Huarui Zhang
    • , Daogang Guan
    • , Baosheng Guo
    • , Bing He
    • , Fangfei Li
    • , Xiaojuan He
    • , Wandong Zhang
    • , Bao-Ting Zhang
    • , Ge Zhang
    •  & Aiping Lu
  • Article
    | Open Access

    MR-focused ultrasound can be used to transiently open the blood-brain barrier (BBB). Here, the authors report the results of a first-in-human trial on four patients with amyotrophic lateral sclerosis (ALS), showing that the procedure reversibly permeabilised the BBB in the motor cortex without complications, and suggest that the procedure could in the future be used to increase drug delivery in ALS patients.

    • Agessandro Abrahao
    • , Ying Meng
    • , Maheleth Llinas
    • , Yuexi Huang
    • , Clement Hamani
    • , Todd Mainprize
    • , Isabelle Aubert
    • , Chinthaka Heyn
    • , Sandra E. Black
    • , Kullervo Hynynen
    • , Nir Lipsman
    •  & Lorne Zinman
  • Article
    | Open Access

    Enamel is the hardest tissue in the body and has been widely studied, yet aspects of its structure remain unclear. Here, the authors report on a study of the orientation and alignment of enamel crystals and challenge previous assumptions.

    • Elia Beniash
    • , Cayla A. Stifler
    • , Chang-Yu Sun
    • , Gang Seob Jung
    • , Zhao Qin
    • , Markus J. Buehler
    •  & Pupa U. P. A. Gilbert
  • Article
    | Open Access

    HuR is an RNA-binding protein that regulates myotube differentiation in vitro. Here, the authors show that the muscle-specific ablation of HuR in mice leads to enhanced endurance capacity and an increase in oxidative fibres by destabilising PGC1α-mRNA, and show that the mice are protected against cancer cachexia

    • Brenda Janice Sánchez
    • , Anne-Marie K. Tremblay
    • , Jean-Philippe Leduc-Gaudet
    • , Derek T. Hall
    • , Erzsebet Kovacs
    • , Jennifer F. Ma
    • , Souad Mubaid
    • , Patricia L. Hallauer
    • , Brittany L. Phillips
    • , Katherine E. Vest
    • , Anita H. Corbett
    • , Dimitris L. Kontoyiannis
    • , Sabah N. A. Hussain
    • , Kenneth E. M. Hastings
    • , Sergio Di Marco
    •  & Imed-Eddine Gallouzi
  • Perspective
    | Open Access

    No effective therapies exist for dry age-related macular degeneration. In this perspective, the authors propose that research should emphasize system biology approaches that integrate various ‘omics’ data into mathematical models to establish pathogenic mechanisms on which to design novel treatments, and identify biomarkers that predict disease progression and therapeutic response.

    • James T. Handa
    • , Cathy Bowes Rickman
    • , Andrew D. Dick
    • , Michael B. Gorin
    • , Joan W. Miller
    • , Cynthia A. Toth
    • , Marius Ueffing
    • , Marco Zarbin
    •  & Lindsay A. Farrer
  • Article
    | Open Access

    Denervation leads to muscle atrophy and neuromuscular endplate remodeling. Here, the authors show that a balanced activation of mTORC1 contributes to the dynamic regulation of autophagic flux in denervated muscle and that activation of PKB/Akt promotes the nuclear import of HDAC4, which is essential for endplate maintenance upon nerve injury

    • Perrine Castets
    • , Nathalie Rion
    • , Marine Théodore
    • , Denis Falcetta
    • , Shuo Lin
    • , Markus Reischl
    • , Franziska Wild
    • , Laurent Guérard
    • , Christopher Eickhorst
    • , Marielle Brockhoff
    • , Maitea Guridi
    • , Chikwendu Ibebunjo
    • , Joseph Cruz
    • , Michael Sinnreich
    • , Rüdiger Rudolf
    • , David J. Glass
    •  & Markus A. Rüegg
  • Article
    | Open Access

    Iatrogenic injury of the ureters is a feared complication of laparoscopic abdominal surgery. Here the authors present the NIR fluorophore ZW800-1 as an intraoperative imaging agent for ureter mapping, showing its safety, pharmacokinetic properties, and efficacy in healthy volunteers and patients undergoing abdominopelvic surgery.

    • Kim S. de Valk
    • , Henricus J. Handgraaf
    • , Marion M. Deken
    • , Babs G. Sibinga Mulder
    • , Adrianus R. Valentijn
    • , Anton G. Terwisscha van Scheltinga
    • , Joeri Kuil
    • , Michiel J. van Esdonk
    • , Jaap Vuijk
    • , Rob F. Bevers
    • , Koen C. Peeters
    • , Fabian A. Holman
    • , John V. Frangioni
    • , Jacobus Burggraaf
    •  & Alexander L. Vahrmeijer
  • Article
    | Open Access

    Bone regeneration is of interest for treating a wide range of medical conditions. Here, the authors report on bioinspired matrix vesicles loaded with black phosphorus nanosheets and cell-specific aptamers for bone regeneration and demonstrate bone defect repair in vivo.

    • Yingqian Wang
    • , Xiaoxia Hu
    • , Lingling Zhang
    • , Chunli Zhu
    • , Jie Wang
    • , Yingxue Li
    • , Yulan Wang
    • , Can Wang
    • , Yufeng Zhang
    •  & Quan Yuan
  • Article
    | Open Access

    Fibrosis is a hallmark of several cardiac pathologies and its underlying mechanisms are still poorly defined. Here the authors show that macrophage hypoxia signaling following transverse aortic constriction in mice suppresses the activation of cardiac fibroblasts by secreting oncostatin M.

    • Hajime Abe
    • , Norihiko Takeda
    • , Takayuki Isagawa
    • , Hiroaki Semba
    • , Satoshi Nishimura
    • , Masaki Suimye Morioka
    • , Yu Nakagama
    • , Tatsuyuki Sato
    • , Katsura Soma
    • , Katsuhiro Koyama
    • , Masaki Wake
    • , Manami Katoh
    • , Masataka Asagiri
    • , Michael L. Neugent
    • , Jung-whan Kim
    • , Christian Stockmann
    • , Tomo Yonezawa
    • , Ryo Inuzuka
    • , Yasushi Hirota
    • , Koji Maemura
    • , Takeshi Yamashita
    • , Kinya Otsu
    • , Ichiro Manabe
    • , Ryozo Nagai
    •  & Issei Komuro
  • Article
    | Open Access

    A number of therapeutic agents aimed at reducing pathology in Duchenne muscular dystrophy have been developed, but may have off-target effects when delivered systemically. Here, the authors express the therapeutic LIF transgene in leukocytes, and show this results in targeting to inflamed dystrophic muscle and reduced fibrosis by suppressing type 2 immunity.

    • Steven S. Welc
    • , Ivan Flores
    • , Michelle Wehling-Henricks
    • , Julian Ramos
    • , Ying Wang
    • , Carmen Bertoni
    •  & James G. Tidball
  • Article
    | Open Access

    In vivo decorporation of U(VI) from bones is an unsolved challenge because of the formation of stable uranium phosphate complexes. Here, the authors develop a hydroxypyridonone-based ligand with strong uranium complexation and low cytotoxicity. They find this ligand effectively removes uranium from kidney and bones in mice, and is suitable for oral administration.

    • Xiaomei Wang
    • , Xing Dai
    • , Cen Shi
    • , Jianmei Wan
    • , Mark A. Silver
    • , Linjuan Zhang
    • , Lanhua Chen
    • , Xuan Yi
    • , Bizheng Chen
    • , Duo Zhang
    • , Kai Yang
    • , Juan Diwu
    • , Jianqiang Wang
    • , Yujie Xu
    • , Ruhong Zhou
    • , Zhifang Chai
    •  & Shuao Wang
  • Article
    | Open Access

    Muscle loss is associated with altered expression of proteins involved in mitochondrial homeostasis, but whether this is causative remains unclear. Here, the authors show that genetic ablation of the pro-fission protein DRP1 leads to accumulation of abnormal mitochondria that induce muscle atrophy by altering Ca2+ homeostasis and cellular stress responses.

    • Giulia Favaro
    • , Vanina Romanello
    • , Tatiana Varanita
    • , Maria Andrea Desbats
    • , Valeria Morbidoni
    • , Caterina Tezze
    • , Mattia Albiero
    • , Marta Canato
    • , Gaia Gherardi
    • , Diego De Stefani
    • , Cristina Mammucari
    • , Bert Blaauw
    • , Simona Boncompagni
    • , Feliciano Protasi
    • , Carlo Reggiani
    • , Luca Scorrano
    • , Leonardo Salviati
    •  & Marco Sandri
  • Article
    | Open Access

    Arthroplasty is the main clinical option for the treatment of osteoarticular lesions, but has limited efficacy. Here, the authors use a wound dressing with autologous mesenchymal stromal cells, functionalised for local BMP2 delivery, and show feasibility and safety in standardised preclinical tests in animal models, suggesting suitability for use in clinical trials.

    • Laetitia Keller
    • , Luc Pijnenburg
    • , Ysia Idoux-Gillet
    • , Fabien Bornert
    • , Laila Benameur
    • , Maryam Tabrizian
    • , Pierrick Auvray
    • , Philippe Rosset
    • , Rosa María Gonzalo-Daganzo
    • , Enrique Gómez Barrena
    • , Luca Gentile
    •  & Nadia Benkirane-Jessel
  • Article
    | Open Access

    Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.

    • Hui-Hui Guo
    • , Chen-Lin Feng
    • , Wen-Xuan Zhang
    • , Zhi-Gang Luo
    • , Hong-Juan Zhang
    • , Ting-Ting Zhang
    • , Chen Ma
    • , Yun Zhan
    • , Rui Li
    • , Song Wu
    • , Zeper Abliz
    • , Cong Li
    • , Xiao-Lin Li
    • , Xiao-Lei Ma
    • , Lu-Lu Wang
    • , Wen-Sheng Zheng
    • , Yan-Xing Han
    •  & Jian-Dong Jiang
  • Article
    | Open Access

    Control of macrophage adhesion and phenotype is important to biomaterial applications. Here, the authors report on the use of bisphosphonate coated gold nanoparticles by magnesium coordination for the controlled adhesion and polarisation of macrophages in vitro and in vivo and controlled cell release.

    • Heemin Kang
    • , Boguang Yang
    • , Kunyu Zhang
    • , Qi Pan
    • , Weihao Yuan
    • , Gang Li
    •  & Liming Bian
  • Article
    | Open Access

    Excessive mechanical stress promotes the development of osteoarthritis. Here Chang et al. identify gremlin-1 as a factor expressed in chondrocytes in response to mechanical stress, and contributing to osteoarthritis via activation of the NF-κB pathway.

    • Song Ho Chang
    • , Daisuke Mori
    • , Hiroshi Kobayashi
    • , Yoshifumi Mori
    • , Hideki Nakamoto
    • , Keita Okada
    • , Yuki Taniguchi
    • , Shurei Sugita
    • , Fumiko Yano
    • , Ung-il Chung
    • , Joo-ri Kim-Kaneyama
    • , Motoko Yanagita
    • , Aris Economides
    • , Ernesto Canalis
    • , Di Chen
    • , Sakae Tanaka
    •  & Taku Saito
  • Article
    | Open Access

    Following muscle damage, an inflammatory response is associated to activation of satellite cells, which drive muscle repair. Here, the authors show that upregulation of Zeb1 in macrophages and muscle fibres regulates inflammation, and also show a role for Zeb1 in maintenance of satellite cell quiescence.

    • Laura Siles
    • , Chiara Ninfali
    • , Marlies Cortés
    • , Douglas S. Darling
    •  & Antonio Postigo
  • Article
    | Open Access

    Parathyroid hormone (PTH) is used to treat osteoporosis, but its therapeutic mechanism remains unclear. Here, the authors show that Tgif1 is a PTH target gene, and that its deletion impairs the function of osteoblasts and PTH-induced bone formation in mice.

    • Hiroaki Saito
    • , Andreas Gasser
    • , Simona Bolamperti
    • , Miki Maeda
    • , Levi Matthies
    • , Katharina Jähn
    • , Courtney L. Long
    • , Hartmut Schlüter
    • , Marcel Kwiatkowski
    • , Vaibhav Saini
    • , Paola Divieti Pajevic
    • , Teresita Bellido
    • , Andre J. van Wijnen
    • , Khalid S. Mohammad
    • , Theresa A. Guise
    • , Hanna Taipaleenmäki
    •  & Eric Hesse
  • Article
    | Open Access

    Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be targeted to specific sub-organ locations in preclinical models and alter the response of metabolic and inflammatory neural pathways.

    • Victoria Cotero
    • , Ying Fan
    • , Tea Tsaava
    • , Adam M. Kressel
    • , Ileana Hancu
    • , Paul Fitzgerald
    • , Kirk Wallace
    • , Sireesha Kaanumalle
    • , John Graf
    • , Wayne Rigby
    • , Tzu-Jen Kao
    • , Jeanette Roberts
    • , Chitresh Bhushan
    • , Suresh Joel
    • , Thomas R. Coleman
    • , Stavros Zanos
    • , Kevin J. Tracey
    • , Jeffrey Ashe
    • , Sangeeta S. Chavan
    •  & Christopher Puleo
  • Article
    | Open Access

    The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.

    • Christian F. Guerrero-Juarez
    • , Priya H. Dedhia
    • , Suoqin Jin
    • , Rolando Ruiz-Vega
    • , Dennis Ma
    • , Yuchen Liu
    • , Kosuke Yamaga
    • , Olga Shestova
    • , Denise L. Gay
    • , Zaixin Yang
    • , Kai Kessenbrock
    • , Qing Nie
    • , Warren S. Pear
    • , George Cotsarelis
    •  & Maksim V. Plikus
  • Article
    | Open Access

    Mammalian joints have poor regenerative capacity following amputation. Here, the authors show that in mice, stimulation of the amputation wound with BMP2 and BMP9 stimulates regeneration of a synovial joint that includes bone, cartilage and a synovial cavity.

    • Ling Yu
    • , Lindsay A. Dawson
    • , Mingquan Yan
    • , Katherine Zimmel
    • , Yu-Lieh Lin
    • , Connor P. Dolan
    • , Manjong Han
    •  & Ken Muneoka
  • Article
    | Open Access

    Insulin resistance is associated with development of type 2 diabetes. Here the authors show that TAZ interacts with c-Jun and Tead4, inducing expression of the insulin receptor substrate 1 (IRS1) leading to increased glucose uptake in muscle, and that its activity is counteracted by statin administration.

    • Jun-Ha Hwang
    • , A Rum Kim
    • , Kyung Min Kim
    • , Jung Il Park
    • , Ho Taek Oh
    • , Sung A Moon
    • , Mi Ran Byun
    • , Hana Jeong
    • , Hyo Kyung Kim
    • , Michael B. Yaffe
    • , Eun Sook Hwang
    •  & Jeong-Ho Hong
  • Article
    | Open Access

    Mutations in the mechanotransduction channel component TMC1/2 cause deafness. Here, the authors use a synthetic AAV to replace TMC1 and 2 in the inner ear and show restoration of cochlear and vestibular function, of neuronal reponses in the auditory cortex and of hearing and balance in mice.

    • Carl A. Nist-Lund
    • , Bifeng Pan
    • , Amy Patterson
    • , Yukako Asai
    • , Tianwen Chen
    • , Wu Zhou
    • , Hong Zhu
    • , Sandra Romero
    • , Jennifer Resnik
    • , Daniel B. Polley
    • , Gwenaelle S. Géléoc
    •  & Jeffrey R. Holt
  • Article
    | Open Access

    Osteoarthritis (OA) is associated with cartilage degeneration, and no effective therapy exists. Here, the authors show that the HPIP protein modulates OA progression by regulating Wnt signaling, and that its knockdown in joints via AAV-mediated gene silencing attentuates pathology.

    • Quanbo Ji
    • , Xiaojie Xu
    • , Lei Kang
    • , Yameng Xu
    • , Jingbo Xiao
    • , Stuart B. Goodman
    • , Xiang Zhu
    • , Wenchao Li
    • , Juan Liu
    • , Xu Gao
    • , Zhifeng Yan
    • , Yuxuan Zheng
    • , Zheng Wang
    • , William J. Maloney
    • , Qinong Ye
    •  & Yan Wang
  • Article
    | Open Access

    Osteoarthritis is characterised by degeneration of joint cartilage. Here the authors show that the RNA-binding protein ZFP36L1 is upregulated in chondrocytes of humans and mice with osteoarthritis, and that its knockdown in mouse joints protects chondrocytes against apoptosis by modulating the function of heat shock proteins.

    • Young-Ok Son
    • , Hyo-Eun Kim
    • , Wan-Su Choi
    • , Churl-Hong Chun
    •  & Jang-Soo Chun
  • Article
    | Open Access

    The human stomach is divided into seven anatomically distinct regions but their protein composition is largely unknown. Here, the authors present a region-resolved map of the healthy human stomach mucosa as well as mucosa proteomes of tumor and tumor nearby tissue from gastric cancer patients.

    • Xiaotian Ni
    • , Zhaoli Tan
    • , Chen Ding
    • , Chunchao Zhang
    • , Lan Song
    • , Shuai Yang
    • , Mingwei Liu
    • , Ru Jia
    • , Chuanhua Zhao
    • , Lei Song
    • , Wanlin Liu
    • , Quan Zhou
    • , Tongqing Gong
    • , Xianju Li
    • , Yanhong Tai
    • , Weimin Zhu
    • , Tieliu Shi
    • , Yi Wang
    • , Jianming Xu
    • , Bei Zhen
    •  & Jun Qin
  • Article
    | Open Access

    Optogenetics is a promising alternative approach for restoration of neuromuscular function. Here the authors establish a closed-loop functional optogenetic stimulation for the control of limb joint angle in murine models, which demonstrates improved control and less fatigue than electrical stimulation systems.

    • Shriya S. Srinivasan
    • , Benjamin E. Maimon
    • , Maurizio Diaz
    • , Hyungeun Song
    •  & Hugh M. Herr
  • Article
    | Open Access

    A role for Slit/Robo signalling in pancreas development has not been defined. Here, the authors generate Robo1/Robo2 knockout mice to identify both as needed for establishing initial pancreatic cell identity as well as for proliferation and survival of pancreatic progenitors.

    • Sophie Escot
    • , David Willnow
    • , Heike Naumann
    • , Silvia Di Francescantonio
    •  & Francesca M. Spagnoli
  • Article
    | Open Access

    SLIT-ROBO alterations arise in pancreatic ductal adenocarcinoma (PDAC), but their role in the pancreas is unclear. Here, the authors use mouse models to show that loss of epithelial Robo2 activates the neighbouring stroma via TGF-β signalling; findings  are relevant to PDAC patients, where ROBO expression correlates with survival outcomes.

    • Andreia V. Pinho
    • , Mathias Van Bulck
    • , Lorraine Chantrill
    • , Mehreen Arshi
    • , Tatyana Sklyarova
    • , David Herrmann
    • , Claire Vennin
    • , David Gallego-Ortega
    • , Amanda Mawson
    • , Marc Giry-Laterriere
    • , Astrid Magenau
    • , Gunther Leuckx
    • , Luc Baeyens
    • , Anthony J. Gill
    • , Phoebe Phillips
    • , Paul Timpson
    • , Andrew V. Biankin
    • , Jianmin Wu
    •  & Ilse Rooman
  • Article
    | Open Access

    Myoblast fusion in skeletal muscle is a complex process but how this is regulated is unclear. Here, the authors identify Ash1L, a histone methyltransferase, as modulating myoblast fusion via activation of the myogenesis gene Cdon, and observe decreased Ash1L expression in Duchenne muscular dystrophy.

    • Ilaria Castiglioni
    • , Roberta Caccia
    • , Jose Manuel Garcia-Manteiga
    • , Giulia Ferri
    • , Giuseppina Caretti
    • , Ivan Molineris
    • , Kenichi Nishioka
    •  & Davide Gabellini
  • Article
    | Open Access

    Vascular smooth muscle cell (VSMC) accumulation is associated with cardiovascular disease. Here, the authors combine single-cell RNA sequencing with lineage labelling to profile VSMC heterogeneity in healthy mice. They show that upregulation of Sca1 in a rare VSMC subpopulation marks a cell phenotype that is prevalent in disease.

    • Lina Dobnikar
    • , Annabel L. Taylor
    • , Joel Chappell
    • , Phoebe Oldach
    • , Jennifer L. Harman
    • , Erin Oerton
    • , Elaine Dzierzak
    • , Martin R. Bennett
    • , Mikhail Spivakov
    •  & Helle F. Jørgensen
  • Article
    | Open Access

    Inflammatory bowel disease is characterised by epithelial dysfunction. Here the authors show that loss of the nuclear receptor LRH-1 leads to epithelial disruption by altering Notch signaling in mouse intestinal organoids, and that LRH-1 overexpression ameliorates immune-mediated colitis in a mouse model.

    • James R. Bayrer
    • , Hongtao Wang
    • , Roy Nattiv
    • , Miyuki Suzawa
    • , Hazel S. Escusa
    • , Robert J. Fletterick
    • , Ophir D. Klein
    • , David D. Moore
    •  & Holly A. Ingraham
  • Article
    | Open Access

    The majority of scoliosis is considered idiopathic with onset in adolescence (AIS) and has a genetic contribution. Here, the authors perform an exome wide association study of data from 457 severe AIS cases and 987 controls, and find a missense variant in SLC39A8 is associated with AIS.

    • Gabe Haller
    • , Kevin McCall
    • , Supak Jenkitkasemwong
    • , Brooke Sadler
    • , Lilian Antunes
    • , Momchil Nikolov
    • , Julia Whittle
    • , Zachary Upshaw
    • , Jimann Shin
    • , Erin Baschal
    • , Carlos Cruchaga
    • , Matthew Harms
    • , Cathleen Raggio
    • , Jose A. Morcuende
    • , Philip Giampietro
    • , Nancy H. Miller
    • , Carol Wise
    • , Ryan S. Gray
    • , Lila Solnica-Krezel
    • , Mitchell Knutson
    • , Matthew B. Dobbs
    •  & Christina A. Gurnett
  • 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
    • , Meena Subramaniam
    • , Nathaniel P. Meyer
    • , Caroline L. Gilchrist
    • , Sarah M. Knox
    • , Aaron D. Tward
    • , Chun J. Ye
    •  & 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
    • , Thomas Clavel
    • , Dirk Haller
    • , Gabriele Hörmannsperger
    • , Hongsup Yoon
    • , Daniela Kolmeder
    • , Alexander Sigruener
    • , Sabrina Krautbauer
    • , Claudine Seeliger
    • , Alexandra Ganzha
    • , Sabine Schweizer
    • , Rosalie Morisset
    • , Till Strowig
    • , Hannelore Daniel
    • , Dominic Helm
    • , Bernhard Küster
    • , Jan Krumsiek
    •  & 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
    • , Usue Etxaniz
    • , Magda Passafaro
    • , Amy Cortez
    • , Chiara Nicoletti
    • , Lorenzo Giordani
    • , Alessio Torcinaro
    • , Marco De Bardi
    • , Silvio Bicciato
    • , Francesca De Santa
    • , Luca Madaro
    •  & Pier Lorenzo Puri