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| Open AccessTbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration
It is not clear if it is the embryonic origin or anatomical location of cardiomyocytes that restrict their contribution to zebrafish heart regeneration. Here, the authors show a plasticity of embryonic precursors following tbx5a fate mapping and that trabecular cardiomyocytes help to rebuild the cortical myocardium.
- Héctor Sánchez-Iranzo
- , María Galardi-Castilla
- & Nadia Mercader
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| Open AccessReading and editing the Pleurodeles waltl genome reveals novel features of tetrapod regeneration
The Iberian ribbed newt Pleurodeles waltl has a wide spectrum of regeneration abilities. Here, Elewa et al. sequence its ~20 Gb genome and transcriptome to investigate the molecular features underlying its regenerative capacities.
- Ahmed Elewa
- , Heng Wang
- & András Simon
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| Open AccessEfficient transgenesis and annotated genome sequence of the regenerative flatworm model Macrostomum lignano
Regeneration capable flatworms have emerged as powerful models for studying stem cell biology and patterning, however their study has been hindered by the lack of transgenesis methods. Here, the authors describe a transgenesis method for Macrostomum lignano, as well as a new annotated genome sequence.
- Jakub Wudarski
- , Daniil Simanov
- & Eugene Berezikov
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| Open AccessGli1 identifies osteogenic progenitors for bone formation and fracture repair
Skeletal progenitors in postnatal mice are highly heterogeneous. Using lineage tracing and RNA-seq the authors show that Gli1+ cells give rise to all osteoblasts in mice, including those required for healing of bone fractures.
- Yu Shi
- , Guangxu He
- & Fanxin Long
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| Open AccessMicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors
Mesodermal iPSC-derived progenitors (MiPs) can regenerate both skeletal and cardiac muscle. Here, the authors show that a microRNA cocktail stimulates skeletal muscle differentiation and that human MiPs can engraft into striated muscle in mice.
- Giorgia Giacomazzi
- , Bryan Holvoet
- & Maurilio Sampaolesi
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| Open AccessHGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells
Organ regeneration by transplantation of ESC/iPSC-derived tissues is a promising but still challenging approach. Here Lin et al. show that liver damage caused by a chemical insult induces not only fibrosis but also Lgr5+ cell expansion that can be further promoted by treatment with HGF/R-spondin1.
- Yuan Lin
- , Zhe-Ping Fang
- & Wei-Jie Zhou
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| Open AccessThe careg element reveals a common regulation of regeneration in the zebrafish myocardium and fin
Common mechanisms underlie organ regeneration, but it is unclear if the same regulatory elements are activated in distinct cells, such as cardiomyocytes and fibroblasts. Here, the authors identify actgfa upstream sequence, called careg, induced by TGFb/Activin during zebrafish heart and fin regeneration.
- Catherine Pfefferli
- & Anna Jaźwińska
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| Open AccessDefining stem cell dynamics and migration during wound healing in mouse skin epidermis
Wound healing is essential to repair the skin after injury and distinct stem cells in the epidermis are known to contribute to the process. Here the authors perform molecular, functional and clonal analysis and reveal the individual contribution of stem cells coming from different epidermal compartments to the wound-healing process in mice.
- Mariaceleste Aragona
- , Sophie Dekoninck
- & Cédric Blanpain
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| Open AccessChromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish
The adult zebrafish heart is capable of regeneration but the molecular mechanisms are poorly understood. Here the authors show that chromatin remodeling factor Brg1 represses cyclin-dependent kinase inhibitors to promote myocardial regeneration.
- Chenglu Xiao
- , Lu Gao
- & Jing-Wei Xiong
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| Open AccessTetrapod limb and sarcopterygian fin regeneration share a core genetic programme
Salamanders are unique among extant tetrapods for their ability to completely regenerate their limbs. Here, Nogueira and colleagues show that lungfishes, the sister clade of tetrapods, regenerate their fins using analogous gene regulatory changes and morphological steps.
- Acacio F. Nogueira
- , Carinne M. Costa
- & Igor Schneider
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| Open AccessExploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury
A potentially superior tissue regenerative strategy to stem cell transplantation is modulation of endogenous stem cells. Here the authors show fibrocartilage stem cells exist in the temporomandibular joint that contribute to cartilage regeneration and can be manipulated to enhance regeneration through canonical Wnt signalling.
- Mildred C. Embree
- , Mo Chen
- & Jeremy J. Mao
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Article
| Open AccessKRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis
It is unclear whether there is a progenitor/stem cell in the basal layer of the urothelium in the bladder. Here, the authors identify Keratin14 positive cells that can regenerate the bladder in both a natural and injury-induced manner, and following neoplastic transformation, can give rise to tumours.
- George Papafotiou
- , Varvara Paraskevopoulou
- & Apostolos Klinakis
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| Open AccessComparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals
The extent to which mammals and other vertebrates share similar mechanisms of tissue regeneration is unclear. Here, the authors use an ear punch assay in spiny mice, which regenerate fully, to show blastema formation and mesenchymal cell proliferation as cell cycle regulators p21 and p27 remain cytoplasmic.
- Thomas R. Gawriluk
- , Jennifer Simkin
- & Ashley W. Seifert
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| Open AccessA developmentally regulated switch from stem cells to dedifferentiation for limb muscle regeneration in newts
How limb regeneration in the newt is regulated at a cellular level is much debated. Here, the authors show different mechanisms acting at different developmental stages, namely stem/progenitor cells in larval regeneration and muscle fibres in the blastema regulate limb regeneration after metamorphosis.
- Hibiki Vincent Tanaka
- , Nathaniel Chuen Yin Ng
- & Chikafumi Chiba
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| Open AccessInhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration
TLR and IL-1R1 ligands are danger signals released following tissue injury and during the healing response. Here, the authors show that IL-1β signalling via IL-1R1/MyD88 inhibits the Akt/GSK-3β/β-catenin pathway in mesenchymal stem cells, which suppresses their mobilization, proliferation, and differentiation into osteoblasts, processes necessary for bone regeneration.
- Mikaël M. Martino
- , Kenta Maruyama
- & Shizuo Akira
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| Open AccessStem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration
The suture mesenchyme has been postulated to act as the niche for stem cells for calvarial bones but the identity of the stem cells is unknown. Here, Maruyama et al.suggest that Axin2 expressing cells act as stem cells not only in craniofacial bone development and homeostasis but in injury-induced repair.
- Takamitsu Maruyama
- , Jaeim Jeong
- & Wei Hsu
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G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy
In response to injury, satellite cells (SCs) asymmetrically divide to self-renew and repair muscle. Here the authors show that a cytokine G-CSF is crucial for long-term expansion of activated SCs and muscle regeneration in mice, suggesting that G-CSF treatment may have beneficial effect in Duchenne muscular dystrophy.
- Nozomi Hayashiji
- , Shinsuke Yuasa
- & Keiichi Fukuda
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Plasticity of Hopx+ type I alveolar cells to regenerate type II cells in the lung
Alveoli are the lung’s functional units composed of two major epithelial cell types, type I and type II. Type II cells are adult lung stem cells, but this study shows that differentiated Type I cells can also self-renew and give rise to Type II cells, revealing a bidirectional relationship between lung epithelial cell types.
- Rajan Jain
- , Christina E. Barkauskas
- & Jonathan A. Epstein
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Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle
The balancing apparatus of the inner ear relies on the mechanosensory activity of hair cells (HC), which are poorly regenerated upon loss in adult mammals. Here, the authors show that in newborn mice HC regenerate through proliferation and transdifferentiation of activated striolar supporting cells that express Lgr5.
- Tian Wang
- , Renjie Chai
- & Alan G. Cheng
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Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration
The age-related decline in the regenerative capacity of muscle can be reversed in mice by exposure to young circulation. Elabd et al.identify the hormone, oxytocin, as a potential mediator of this effect, showing that its plasma levels decline with age and that administration of oxytocin to aged mice improves muscle regeneration.
- Christian Elabd
- , Wendy Cousin
- & Irina M. Conboy
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Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2
The re-epithelialization phase in skin wound repair involves epidermal cell migration into the wound, proliferation and differentiation. Here the authors describe a role for the transcription factor Tcf3 and its target, the secreted factor lipocalin2, in cell migration during wound healing in mice.
- Qi Miao
- , Amy T. Ku
- & Hoang Nguyen
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| Open AccessDynamic haematopoietic cell contribution to the developing and adult epicardium
The murine epicardium forms an envelope around the heart and contains cells that can participate in cardiac repair. Here the authors discover a population of epicardial cells derived from blood cells, which proliferate and change their surrounding extracellular matrix in response to cardiac injury.
- Gemma M. Balmer
- , Sveva Bollini
- & Paul R. Riley
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Knockdown and knockout of β1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling
Integrin signalling has been implicated in liver regeneration but the molecular processes are not well understood. Here the authors show that β1-integrin is required for liver regeneration and that its absence impairs ligand-induced activation of the epidermal growth factor receptor in mice.
- Tobias Speicher
- , Beat Siegenthaler
- & Sabine Werner
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| Open AccessComplement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration
Components of the complement system have been shown to promote liver regeneration. Haynes et al. demonstrate that the complement fragment C3a can induce regeneration of the embryonic chick retina from stem and progenitor cells of the ciliary margin via activation of STAT3 and other downstream signalling pathways.
- Tracy Haynes
- , Agustin Luz-Madrigal
- & Katia Del Rio-Tsonis
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Collagen VI regulates satellite cell self-renewal and muscle regeneration
Satellite cells have important roles in homeostasis and regeneration of skeletal muscles. Urciuolo et al. show that the extracellular matrix protein collagen VI is required for preserving satellite cell self-renewal and muscle regeneration in vitro and in vivoby modulating muscle mechanical properties.
- Anna Urciuolo
- , Marco Quarta
- & Paolo Bonaldo
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Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81
The skeletal muscle has a remarkable capacity to regenerate after injury. Here Charrin et al. reveal that restoration of muscle architecture after injury requires a tight control of muscle cell fusion by the tetraspanin proteins CD9 and CD81 through their interaction with the cell surface protein CD9P-1.
- Stéphanie Charrin
- , Mathilde Latil
- & Eric Rubinstein
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DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling
Osteoblasts and endothelial cells have important roles in bone regeneration. Kim and colleagues identify the protein DJ-1 as an angiogenic and osteogenic signalling molecule involved in the cross-talk between these cells and show that DJ-1 promotes bone regeneration and fracture healing in mice.
- Jung-Min Kim
- , Hong-In Shin
- & Pann-Ghill Suh
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Article
| Open AccessPromotion of plasma membrane repair by vitamin E
Membrane repair of myocytes is important to prevent such disease as muscular dystrophy but the properties of this repair are not well characterised. In this study, vitamin E is shown to be important in the repair of myocyte cell membranes in cultured cells and in intact muscle.
- Amber C. Howard
- , Anna K. McNeil
- & Paul L. McNeil
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Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells
The fusion of satellite cells to muscle fibres during adult life is required for both muscle growth and regeneration but it is unknown whether non-muscle cells contribute to this process. Now, Dellavalle and colleagues show that pericytes, cells associated with the vasculature can contribute to both growth and regeneration of muscle fibres.
- A. Dellavalle
- , G. Maroli
- & G. Cossu
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| Open AccessRegenerative capacity in newts is not altered by repeated regeneration and ageing
Tissue regeneration is of great interest; however the number of times a given tissue can regenerate is unknown. Now, Eguchiet al. demonstrate that the lens of the Japanese newt—Cynops pyrrhogaster—can regenerate 18 times over a 16-year period, and that the new lenses are similar to those of control adult animals.
- Goro Eguchi
- , Yukiko Eguchi
- & Panagiotis A. Tsonis
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Human TSC2-null fibroblast-like cells induce hair follicle neogenesis and hamartoma morphogenesis
Mutations inTSC2 lead to the formation of benign tumours called hamartomas. In this study, using a mouse xenograft model, the authors demonstrate that fibroblasts from patients carrying TSC2mutations can induce keratinocytes to form both hair follicles and hamartoma-like growths with active mTOR signalling.
- Shaowei Li
- , Rajesh L. Thangapazham
- & Thomas N. Darling