Reprogramming articles within Nature Communications

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  • Article
    | Open Access

    Fibroblasts can be directly reprogrammed to cardiomyocytes, but reprogramming is less efficient for adult compared to embryonic fibroblasts. Here, the authors find that inhibition of inflammation and Cox-2-prostaglandin-cAMP-IL-1β signaling enhances reprogramming efficiency of adult, but not embryonic fibroblasts.

    • Naoto Muraoka
    • , Kaori Nara
    •  & Masaki Ieda

  • Article
    | Open Access

    Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.

    • Maria Clara Guida
    • , Ryan Tyge Birse
    •  & Rolf Bodmer

  • Article
    | Open Access

    HMGN1 and HMGN2 are ubiquitous nucleosome binding proteins. Here the authors provide evidence that HMGN proteins preferentially localize to chromatin regulatory sites to modulate the plasticity of the epigenetic landscape, proposing that HGMNs stabilize, rather than determine, cell identity.

    • Bing He
    • , Tao Deng
    •  & Michael Bustin

  • Article
    | Open Access

    In vitro culture has detrimental effects on transcriptomes and epigenetic programming of zygotes. Here the authors use microfluidic technology to co-culture bovine oviduct epithelial cells with zygotes and show that the transcriptomes and global methylation patterns of these zygotes are more similar to in vivo zygotes than to conventionally cultured zygotes.

    • Marcia A. M. M. Ferraz
    • , Hoon Suk Rho
    •  & Bart M. Gadella

  • Article
    | Open Access

    In vivo reprogramming of somatic cells is hampered by the need for vectors to express the OKSM factors in selected organs. Here the authors report new AAV-based vectors capable of in vivo reprogramming at low doses.

    • Elena Senís
    • , Lluc Mosteiro
    •  & Dirk Grimm

  • Article
    | Open Access

    CRISPRa is an attractive tool for cellular reprogramming due to its multiplexing capacity and direct targeting of genomic loci. Here the authors demonstrate the reprogramming of human fibroblasts into iPSCs, which is enhanced by targeting a conserved Alu-motif.

    • Jere Weltner
    • , Diego Balboa
    •  & Timo Otonkoski

  • Article
    | Open Access

    Uhrf1 is a known regulator of heterochromatin and DNA methylation in embryonic stem cells (ESCs). Here, the authors demonstrate that Uhrf1 acts together with the Set1/COMPASS complex regulator of active transcription to promote H3K4 methylation at bivalent loci and Uhrf1 loss results in disruption of differentiation.

    • Kun-Yong Kim
    • , Yoshiaki Tanaka
    •  & In-Hyun Park

  • Article
    | Open Access

    Sex differences in placental O-linked N-acetylglucosamine transferase (OGT) activity mediate the effects of prenatal stress on neurodevelopmental programming. Here authors provide evidence that OGT confers variation in vulnerability to prenatal insults by establishing sex-specific trophoblast gene expression via regulation of H3K27me3.

    • Bridget M. Nugent
    • , Carly M. O’Donnell
    •  & Tracy L. Bale

  • Article
    | Open Access

    Histone variant H3.3 is incorporated at transcriptionally active genes and is associated with active marks. Here, the authors investigate H3.3 deposition during reprogramming and find that initially H3.3 helps maintain parental cell fate and is later required for establishment of the cell lineages.

    • Hai-Tong Fang
    • , Chadi A. EL Farran
    •  & Yuin-Han Loh

  • Article
    | Open Access

    Induced pluripotent stem cells (iPSCs) have potential for regenerative medicine applications, but are generated with very low efficiency. Here, the authors show highly efficient reprogramming of human primary fibroblasts to iPSCs via the synergistic activity of synthetic modified mRNAs, mature miRNA mimics, and optimized culture methods.

    • Igor Kogut
    • , Sandra M. McCarthy
    •  & Ganna Bilousova

  • Article
    | Open Access

    The T-box transcription factor eomesodermin (EOMES) acts both in endoderm specification as well as heart development, suggesting context-specific function. Here, the authors show that dose-controlled EOMES induction is sufficient for cardiogenic programming of human pluripotent stem cells.

    • Martin J. Pfeiffer
    • , Roberto Quaranta
    •  & Boris Greber

  • Article
    | Open Access

    Derivation of human induced pluripotent stem cells (hiPSCs) produces primed hiPSCs that can in turn be converted to naive hiPSCs. Here, the authors directly reprogram somatic cells to form both naive and primed isogenic hiPSCs and confirm the similarity of naive hiPSCs to their in vivo counterparts.

    • Stéphanie Kilens
    • , Dimitri Meistermann
    •  & Matthew L. Albert

  • Article
    | Open Access

    X-chromosome inactivation is reversed in the mouse inner cell mass (ICM) through a mechanism that is not fully understood. Here, the authors investigate this process and characterize the contributions of the epigenetic landscape and transcription factors in X-linked gene reactivation dynamics.

    • Maud Borensztein
    • , Ikuhiro Okamoto
    •  & Edith Heard

  • Article
    | Open Access

    Priming of the adult mouse heart with Tβ4 activates dormant epicardium-derived cells to aid repair of injured myocardium. Here, Vieiraet al. explain this process and show that Tβ4 binds a chromatin remodeller BRG1 and activates Wt1, the key regulator of epicardial epithelial-to-mesenchymal transformation, by altering the epigenetic landscape of the Wt1 locus.

    • Joaquim Miguel Vieira
    • , Sara Howard
    •  & Paul R. Riley

  • Article
    | Open Access

    Tumour-specific T cells can be expandedin vitroand adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.

    • Taisuke Kondo
    • , Rimpei Morita
    •  & Akihiko Yoshimura

  • Article
    | Open Access

    The identification of master regulator genes that may be manipulatedin vitro to regulate reprogramming has been difficult. Here, the authors use a computational systems approach to identify three genes (FoxA1, Nkx3.1and the androgen receptor) that can reprogramme fibroblasts to prostate tissue.

    • Flaminia Talos
    • , Antonina Mitrofanova
    •  & Michael M. Shen

  • Article
    | Open Access

    Liver and pancreas cells arise from a common endoderm progenitor in the embryo, but what regulates their cell fate is unclear. Here, the authors show that expression of the Three-Amino-acid-Loop-Extension (TALE) homeobox TG-interacting factor 2 (TGIF2) in hepatocytes reprogrammes the cells to a pancreatic fate.

    • Nuria Cerdá-Esteban
    • , Heike Naumann
    •  & Francesca M. Spagnoli

  • Article
    | Open Access

    Schwann cells (SCs) myelinate peripheral nerve axons and offer opportunities for the treatment of injuries and demyelinating diseases but reliable and renewable sources of these cells are hard to come by. Here the authors reprogram rat, mouse and human fibroblasts into Schwann cells using two transcription factors.

    • Pietro Giuseppe Mazzara
    • , Luca Massimino
    •  & Vania Broccoli

  • Article
    | Open Access

    Land plants and metazoans are both able to reprogram differentiated cells to stem cells under certain circumstances. Here the authors show that the moss CSP1 protein, which shares conserved domains with the mammalian pluripotent stem cell factor Lin28, promotes reprogramming of leaf cells to apical stem cells.

    • Chen Li
    • , Yusuke Sako
    •  & Mitsuyasu Hasebe

  • Article
    | Open Access

    Reactivation of the inactive X chromosome (Xi) has modelled epigenetic reprogramming in mouse. Here, by using cell fusion between human female fibroblasts and mouse embryonic stem cells, the authors show a complex hierarchy of epigenetic changes that are required to reactivate the genes on the human Xi chromosome.

    • Irene Cantone
    • , Hakan Bagci
    •  & Amanda G. Fisher

  • Article
    | Open Access

    The reprogramming of fibroblasts to pluripotent stem cells has been well documented but there is interest in identifying additional factors involved. Here, the authors perform a screen of human kinases and show that the bromodomain protein, BRD3R, can promote reprogramming and suggest a role for this factor in regulating mitosis.

    • Zhicheng Shao
    • , Ruowen Zhang
    •  & Kejin Hu

  • Article
    | Open Access

    It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al. take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the original fibroblasts, but none convey oncogenic potential.

    • Kunal Bhutani
    • , Kristopher L. Nazor
    •  & Jeanne F. Loring

  • Article
    | Open Access

    The molecular mechanisms regulating skin dermal changes are unclear. Here, the authors show that deletion of Hedgehog (Hh) in the upper dermis alters the response to epidermal Wnt signalling, which, together with changes in extracellular matrix production, influences distinct fibroblast lineages differently.

    • Beate M. Lichtenberger
    • , Maria Mastrogiannaki
    •  & Fiona M. Watt

  • Article
    | Open Access

    Genetic and epigenetic abnormalities have been found to result from reprogramming of differentiated cells into human induced pluripotent stem cells (hiPSCs). Here, Klawitter et al.identify endogenous L1, Alu and SVA mobilization during reprogramming, highlighting the risk of insertional mutagens in hiPSCs.

    • Sabine Klawitter
    • , Nina V. Fuchs
    •  & Gerald G. Schumann

  • Article
    | Open Access

    Understanding human preimplantation development is invaluable for human reproduction and stem cell research. By employing single-cell RNA sequencing in oocytes, zygotes and single blastomeres, Töhönen et al.identify new regulatory factors and sequences that drive early human preimplantation development.

    • Virpi Töhönen
    • , Shintaro Katayama
    •  & Juha Kere

  • Article
    | Open Access

    Direct reprogramming of cardiac fibroblasts into cardiomyocytes is an attractive strategy for heart regeneration, but it is hampered by the low efficiency of the process. Here the authors show that mouse fibroblasts can be reprogrammed with high efficiency into functional cardiomyocytes when pro-fibrotic signaling is inhibited.

    • Yuanbiao Zhao
    • , Pilar Londono
    •  & Kunhua Song

  • Article
    | Open Access

    Reprogramming holds great promise for regenerative medicine but the molecular mechanisms governing the generation of induced pluripotent stem cells remain unclear. Here, the authors reveal functions for the axonal guidance cue Netrin-1 in constraining apoptosis at the early stage of reprogramming and in established pluripotent cells.

    • Duygu Ozmadenci
    • , Olivier Féraud
    •  & Fabrice Lavial

  • Article
    | Open Access

    Characterizing the cellular stages that lead to induced reprogramming is of much interest and cell surface markers could offer unique advantages for this. Here the authors use surface proteomics and discover CD24 as a marker that tracks reprogramming-responsive cells and enables the analysis and enrichment of transgene-dependent and -independent induced pluriopotent stem cells.

    • Nika Shakiba
    • , Carl A. White
    •  & Peter W Zandstra

  • Article |

    Chronic myeloid leukaemia is characterized by the genetic translocation t(9;22) encoding for BCR-ABL oncogene; however, the molecular mechanisms of disease progression are poorly understood. Here Amabile et al. show that aberrant methylation is promoted by BCR-ABL, driving the evolution of the disease.

    • Giovanni Amabile
    • , Annalisa Di Ruscio
    •  & Daniel G. Tenen

  • Article
    | Open Access

    LIF/STAT3 signalling characterizes naive pluripotency in mouse embryonic stem cells (ESCs), but whether this pathway can sustain a similar state in human cells is not completely understood. Here the authors show that LIF stimulation and enhancement of STAT3 activity allow human ESCs to escape from FGF2 dependency and facilitates their entry into a naive-like state of pluripotency.

    • Hongwei Chen
    • , Irène Aksoy
    •  & Pierre Savatier

  • Article |

    The protein kinase Rio1 is known to promote 40S ribosome formation in the cytoplasm. Using budding yeast, the authors here show that Rio1 also acts in the nucleus, downregulates rDNA transcription by Pol I, and activates the processing of its transcripts to ensure rDNA stability and segregation.

    • Maria G. Iacovella
    • , Cristina Golfieri
    •  & Peter De Wulf

  • Article
    | Open Access

    Improving the efficiency of reprogramming of somatic cells to induced pluripotent stem cells is of major interest. Here, the authors combine ascorbic acid and 2i (MAP kinase and GSK inhibitors) conditions and show increased efficiency and synchronicity in the reprogramming of fibroblasts and partially reprogrammed cells, and study epigenetic effectors and signalling pathways responsible for this effect.

    • Khoa A. Tran
    • , Steven A. Jackson
    •  & Rupa Sridharan

  • Article
    | Open Access

    Reprogramming of mouse somatic cells into iPSCs often generates pre-iPSCs, low-grade iPSCs that show abnormal Dlk1-Dio3 imprinting, and fully reprogrammed, high-grade iPSCs. Here, the authors show that germ-cell marker Dppa3 enhances reprogramming kinetics, critical for the maintenance of Dlk1-Dio3 imprinting and generation of fully reprogrammed iPSCs.

    • Xingbo Xu
    • , Lukasz Smorag
    •  & D. V. Krishna Pantakani

  • Article |

    During somatic cell reprogramming, the cell transits through intermediate states. Here, the authors perform an in-depth quantitative proteomic analysis of the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells and observe two waves of proteome reorganisation.

    • Marco Benevento
    • , Peter D. Tonge
    •  & Albert J. R. Heck

  • Article
    | Open Access

    Various strategies have been reported to generate mouse trophoblast stem cells (TSCs) from mouse embryonic stem cells (ESCs). Here the authors show that, regardless of the strategy used for TSC generation, these retain an epigenetic and transcriptional memory of the ESC origin and the transition remains incomplete.

    • Francesco Cambuli
    • , Alexander Murray
    •  & Myriam Hemberger

  • Article
    | Open Access

    Changes in chromatin structure impact gene expression programs by modulating accessibility to the transcription machinery. Here, West et al. explore differences in nucleosome occupancy between mammalian pluripotent and somatic cells and uncover regulatory regions likely to play key roles in determining cell identity.

    • Jason A. West
    • , April Cook
    •  & Robert E. Kingston

  • Article |

    Loss of function of the kinase PINK1 is associated with familial early-onset Parkinson’s disease and impaired clearance of damaged mitochondria. Here the authors show that the resulting oxidative stress activates the hypoxia regulator HIF1α, resulting in increased glycolysis and cell proliferation.

    • Raquel Requejo-Aguilar
    • , Irene Lopez-Fabuel
    •  & Juan P. Bolaños

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