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  • Models, Biological  (119)
  • Nature Publishing Group (NPG)  (119)
  • 2005-2009  (119)
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  • 1
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    Reprogramming towards pluripotency requires AID-dependent DNA demethylation (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-12-23
    Description: Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (〈0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons (fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly (1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase (AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide new evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutani, Nidhi -- Brady, Jennifer J -- Damian, Mara -- Sacco, Alessandra -- Corbel, Stephane Y -- Blau, Helen M -- AG009521/AG/NIA NIH HHS/ -- AG024987/AG/NIA NIH HHS/ -- AI007328/AI/NIAID NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG024987/AG/NIA NIH HHS/ -- R01 AG024987-05/AG/NIA NIH HHS/ -- T32 AI007328/AI/NIAID NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1042-7. doi: 10.1038/nature08752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20027182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Fusion ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; Chromatin Immunoprecipitation ; Cytidine Deaminase/deficiency/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; DNA Replication ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/*cytology/enzymology/*metabolism ; Lung/cytology/embryology ; Mice ; Models, Biological ; Octamer Transcription Factor-3/genetics ; Promoter Regions, Genetic/genetics ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    Darwin 200: Great expectations (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):317-8. doi: 10.1038/456317a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020598" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anniversaries and Special Events ; Biodiversity ; *Biological Evolution ; Epidemiology/trends ; Humans ; Models, Biological ; Mutagenesis ; Religion and Science ; Science/*trends ; Selection, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    Cancer: Deconstructing oncogenesis (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luo, Ji -- Elledge, Stephen J -- England -- Nature. 2008 Jun 19;453(7198):995-6. doi: 10.1038/453995a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Transformation, Neoplastic/*genetics ; Colonic Neoplasms/genetics/pathology ; Gene Expression Regulation, Neoplastic ; Genes, p53/genetics ; Genes, ras/genetics ; Humans ; Models, Biological ; Oncogenes/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Systems biology: Reverse engineering the cell (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ingolia, Nicholas T -- Weissman, Jonathan S -- England -- Nature. 2008 Aug 28;454(7208):1059-62. doi: 10.1038/4541059a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756243" target="_blank"〉PubMed〈/a〉
    Keywords: *Environment ; Galactose/metabolism ; *Gene Expression Regulation, Fungal/drug effects ; Glucose/metabolism/pharmacology ; Metabolic Networks and Pathways/drug effects/*genetics ; Microfluidics ; Models, Biological ; Osmotic Pressure ; RNA Stability/drug effects ; Saccharomyces cerevisiae/classification/drug effects/*genetics/*metabolism ; Systems Biology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Preserving cell shape under environmental stress (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-02-26
    Description: Maintaining cell shape and tone is crucial for the function and survival of cells and tissues. Mechanotransduction relies on the transformation of minuscule mechanical forces into high-fidelity electrical responses. When mechanoreceptors are stimulated, mechanically sensitive cation channels open and produce an inward transduction current that depolarizes the cell. For this process to operate effectively, the transduction machinery has to retain integrity and remain unfailingly independent of environmental changes. This is particularly challenging for poikilothermic organisms, where changes in temperature in the environment may impact the function of mechanoreceptor neurons. Thus, we wondered how insects whose habitat might quickly vary over several tens of degrees of temperature manage to maintain highly effective mechanical senses. We screened for Drosophila mutants with defective mechanical responses at elevated ambient temperatures, and identified a gene, spam, whose role is to protect the mechanosensory organ from massive cellular deformation caused by heat-induced osmotic imbalance. Here we show that Spam protein forms an extracellular shield that guards mechanosensory neurons from environmental insult. Remarkably, heterologously expressed Spam protein also endowed other cells with superb defence against physically and chemically induced deformation. We studied the mechanical impact of Spam coating and show that spam-coated cells are up to ten times stiffer than uncoated controls. Together, these results help explain how poikilothermic organisms preserve the architecture of critical cells during environmental stress, and illustrate an elegant and simple solution to such challenge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387185/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387185/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, Boaz -- Hardy, Robert W -- McConnaughey, William B -- Zuker, Charles S -- R01 EY006979/EY/NEI NIH HHS/ -- R01 EY006979-18/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 20;452(7185):361-4. doi: 10.1038/nature06603. Epub 2008 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Departments of Neurobiology and Neurosciences, University of California at San Diego, La Jolla, California 92093-0649, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18297055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Shape/*drug effects/*physiology ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*cytology/drug effects/genetics/physiology ; Electrophysiology ; *Environment ; Eye Proteins/genetics/metabolism ; Hot Temperature ; Humidity ; Mechanoreceptors/cytology/physiology ; Mechanotransduction, Cellular/*drug effects/*physiology ; Models, Biological ; Osmotic Pressure ; Stimulation, Chemical ; Stress, Mechanical
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    High-amplitude fluctuations and alternative dynamical states of midges in Lake Myvatn (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-03-07
    Description: Complex dynamics are often shown by simple ecological models and have been clearly demonstrated in laboratory and natural systems. Yet many classes of theoretically possible dynamics are still poorly documented in nature. Here we study long-term time-series data of a midge, Tanytarsus gracilentus (Diptera: Chironomidae), in Lake Myvatn, Iceland. The midge undergoes density fluctuations of almost six orders of magnitude. Rather than regular cycles, however, these fluctuations have irregular periods of 4-7 years, indicating complex dynamics. We fit three consumer-resource models capable of qualitatively distinct dynamics to the data. Of these, the best-fitting model shows alternative dynamical states in the absence of environmental variability; depending on the initial midge densities, the model shows either fluctuations around a fixed point or high-amplitude cycles. This explains the observed complex population dynamics: high-amplitude but irregular fluctuations occur because stochastic variability causes the dynamics to switch between domains of attraction to the alternative states. In the model, the amplitude of fluctuations depends strongly on minute resource subsidies into the midge habitat. These resource subsidies may be sensitive to human-caused changes in the hydrology of the lake, with human impacts such as dredging leading to higher-amplitude fluctuations. Tanytarsus gracilentus is a key component of the Myvatn ecosystem, representing two-thirds of the secondary productivity of the lake and providing vital food resources to fish and to breeding bird populations. Therefore the high-amplitude, irregular fluctuations in midge densities generated by alternative dynamical states dominate much of the ecology of the lake.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ives, Anthony R -- Einarsson, Arni -- Jansen, Vincent A A -- Gardarsson, Arnthor -- England -- Nature. 2008 Mar 6;452(7183):84-7. doi: 10.1038/nature06610.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. arives@wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18322533" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chironomidae/*physiology ; Computer Simulation ; *Ecosystem ; Eukaryota/physiology ; Food ; *Fresh Water ; Iceland ; Models, Biological ; Population Density ; Stochastic Processes
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Developmental biology: order in the lung (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-06-06
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865228/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865228/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warburton, David -- P01 HL060231/HL/NHLBI NIH HHS/ -- P01 HL060231-09/HL/NHLBI NIH HHS/ -- R01 HL044060/HL/NHLBI NIH HHS/ -- R01 HL044977/HL/NHLBI NIH HHS/ -- R01 HL044977-16/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 Jun 5;453(7196):733-5. doi: 10.1038/453733a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18528385" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Body Patterning/genetics/*physiology ; Fibroblast Growth Factor 10/metabolism ; Intracellular Signaling Peptides and Proteins ; Lung/*anatomy & histology/*embryology/metabolism ; Membrane Proteins/metabolism ; Mice ; Models, Biological ; Organogenesis/genetics/*physiology ; Receptor, Fibroblast Growth Factor, Type 2/genetics/metabolism
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    The earliest thymic progenitors for T cells possess myeloid lineage potential (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-04-11
    Description: There exists controversy over the nature of haematopoietic progenitors of T cells. Most T cells develop in the thymus, but the lineage potential of thymus-colonizing progenitors is unknown. One approach to resolving this question is to determine the lineage potentials of the earliest thymic progenitors (ETPs). Previous work has shown that ETPs possess T and natural killer lymphoid potentials, and rare subsets of ETPs also possess B lymphoid potential, suggesting an origin from lymphoid-restricted progenitor cells. However, whether ETPs also possess myeloid potential is unknown. Here we show that nearly all ETPs in adult mice possess both T and myeloid potential in clonal assays. The existence of progenitors possessing T and myeloid potential within the thymus is incompatible with the current dominant model of haematopoiesis, in which T cells are proposed to arise from lymphoid-. Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, J Jeremiah -- Bhandoola, Avinash -- England -- Nature. 2008 Apr 10;452(7188):764-7. doi: 10.1038/nature06840.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401411" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology ; Female ; Granulocytes/cytology ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology/metabolism ; Macrophages/cytology ; Mice ; Models, Biological ; Myeloid Cells/*cytology/metabolism ; Stromal Cells/cytology ; T-Lymphocytes/*cytology/metabolism ; Thymus Gland/*cytology
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Oligopotent stem cells are distributed throughout the mammalian ocular surface (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-10-03
    Description: The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Majo, Francois -- Rochat, Ariane -- Nicolas, Michael -- Jaoude, Georges Abou -- Barrandon, Yann -- England -- Nature. 2008 Nov 13;456(7219):250-4. doi: 10.1038/nature07406. Epub 2008 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne CH, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18830243" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Cattle ; Cells, Cultured ; Child, Preschool ; Clone Cells ; Corneal Transplantation ; Epithelium, Corneal/*cytology/metabolism ; Female ; Gene Expression Regulation ; Humans ; Infant ; Keratinocytes/cytology/metabolism ; Male ; Mice ; Mice, SCID ; Models, Biological ; Multipotent Stem Cells/*cytology ; Proteins/metabolism ; Rats ; Swine
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    The adaptive significance of temperature-dependent sex determination in a reptile (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-01-22
    Description: Understanding the mechanisms that determine an individual's sex remains a primary challenge for evolutionary biology. Chromosome-based systems (genotypic sex determination) that generate roughly equal numbers of sons and daughters accord with theory, but the adaptive significance of environmental sex determination (that is, when embryonic environmental conditions determine offspring sex, ESD) is a major unsolved problem. Theoretical models predict that selection should favour ESD over genotypic sex determination when the developmental environment differentially influences male versus female fitness (that is, the Charnov-Bull model), but empirical evidence for this hypothesis remains elusive in amniote vertebrates--the clade in which ESD is most prevalent. Here we provide the first substantial empirical support for this model by showing that incubation temperatures influence reproductive success of males differently than that of females in a short-lived lizard (Amphibolurus muricatus, Agamidae) with temperature-dependent sex determination. We incubated eggs at a variety of temperatures, and de-confounded sex and incubation temperature by using hormonal manipulations to embryos. We then raised lizards in field enclosures and quantified their lifetime reproductive success. Incubation temperature affected reproductive success differently in males versus females in exactly the way predicted by theory: the fitness of each sex was maximized by the incubation temperature that produces that sex. Our results provide unequivocal empirical support for the Charnov-Bull model for the adaptive significance of temperature-dependent sex determination in amniote vertebrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warner, D A -- Shine, R -- England -- Nature. 2008 Jan 31;451(7178):566-8. doi: 10.1038/nature06519. Epub 2008 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Sydney, Sydney, New South Wales 2006, Australia. dwarner@iastate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18204437" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/physiology ; Adaptation, Physiological/*physiology ; Animals ; Body Size ; Fadrozole/pharmacology ; Female ; Lizards/*embryology/*physiology ; Male ; Models, Biological ; Ovum/drug effects/growth & development ; Reproduction/physiology ; Sex Characteristics ; Sex Differentiation/*physiology ; *Temperature
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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