ALBERT

Beschreibung: Genome sequencing has uncovered a new mutational phenomenon in cancer and congenital disorders called chromothripsis. Chromothripsis is characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes. The mechanism for chromothripsis is unknown, but we previously proposed that it could occur through the physical isolation of chromosomes in aberrant nuclear structures called micronuclei. Here, using a combination of live cell imaging and single-cell genome sequencing, we demonstrate that micronucleus formation can indeed generate a spectrum of genomic rearrangements, some of which recapitulate all known features of chromothripsis. These events are restricted to the mis-segregated chromosome and occur within one cell division. We demonstrate that the mechanism for chromothripsis can involve the fragmentation and subsequent reassembly of a single chromatid from a micronucleus. Collectively, these experiments establish a new mutational process of which chromothripsis is one extreme outcome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742237/" 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/PMC4742237/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Cheng-Zhong -- Spektor, Alexander -- Cornils, Hauke -- Francis, Joshua M -- Jackson, Emily K -- Liu, Shiwei -- Meyerson, Matthew -- Pellman, David -- GM083299-18/GM/NIGMS NIH HHS/ -- R01 GM061345/GM/NIGMS NIH HHS/ -- R01 GM083299/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jun 11;522(7555):179-84. doi: 10.1038/nature14493. Epub 2015 May 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [4] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [3] Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA [4] Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [3] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [4] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26017310" target="_blank"〉PubMed〈/a〉

Beschreibung: The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex and interphase early mitotic inhibitor 1 (Emi1) ensures the correct order and timing of distinct cell-cycle transitions. Here we use cryo-electron microscopy to determine atomic structures of APC/C-coactivator complexes with either Emi1 or a UbcH10-ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10-ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of future experiments to investigate APC/C functions in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608048/" 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/PMC4608048/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Leifu -- Zhang, Ziguo -- Yang, Jing -- McLaughlin, Stephen H -- Barford, David -- A8022/Cancer Research UK/United Kingdom -- MC_UP_1201/6/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2015 Jun 25;522(7557):450-4. doi: 10.1038/nature14471. Epub 2015 Jun 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26083744" target="_blank"〉PubMed〈/a〉

Beschreibung: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530010/" 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/PMC4530010/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roadmap Epigenomics Consortium -- Kundaje, Anshul -- Meuleman, Wouter -- Ernst, Jason -- Bilenky, Misha -- Yen, Angela -- Heravi-Moussavi, Alireza -- Kheradpour, Pouya -- Zhang, Zhizhuo -- Wang, Jianrong -- Ziller, Michael J -- Amin, Viren -- Whitaker, John W -- Schultz, Matthew D -- Ward, Lucas D -- Sarkar, Abhishek -- Quon, Gerald -- Sandstrom, Richard S -- Eaton, Matthew L -- Wu, Yi-Chieh -- Pfenning, Andreas R -- Wang, Xinchen -- Claussnitzer, Melina -- Liu, Yaping -- Coarfa, Cristian -- Harris, R Alan -- Shoresh, Noam -- Epstein, Charles B -- Gjoneska, Elizabeta -- Leung, Danny -- Xie, Wei -- Hawkins, R David -- Lister, Ryan -- Hong, Chibo -- Gascard, Philippe -- Mungall, Andrew J -- Moore, Richard -- Chuah, Eric -- Tam, Angela -- Canfield, Theresa K -- Hansen, R Scott -- Kaul, Rajinder -- Sabo, Peter J -- Bansal, Mukul S -- Carles, Annaick -- Dixon, Jesse R -- Farh, Kai-How -- Feizi, Soheil -- Karlic, Rosa -- Kim, Ah-Ram -- Kulkarni, Ashwinikumar -- Li, Daofeng -- Lowdon, Rebecca -- Elliott, GiNell -- Mercer, Tim R -- Neph, Shane J -- Onuchic, Vitor -- Polak, Paz -- Rajagopal, Nisha -- Ray, Pradipta -- Sallari, Richard C -- Siebenthall, Kyle T -- Sinnott-Armstrong, Nicholas A -- Stevens, Michael -- Thurman, Robert E -- Wu, Jie -- Zhang, Bo -- Zhou, Xin -- Beaudet, Arthur E -- Boyer, Laurie A -- De Jager, Philip L -- Farnham, Peggy J -- Fisher, Susan J -- Haussler, David -- Jones, Steven J M -- Li, Wei -- Marra, Marco A -- McManus, Michael T -- Sunyaev, Shamil -- Thomson, James A -- Tlsty, Thea D -- Tsai, Li-Huei -- Wang, Wei -- Waterland, Robert A -- Zhang, Michael Q -- Chadwick, Lisa H -- Bernstein, Bradley E -- Costello, Joseph F -- Ecker, Joseph R -- Hirst, Martin -- Meissner, Alexander -- Milosavljevic, Aleksandar -- Ren, Bing -- Stamatoyannopoulos, John A -- Wang, Ting -- Kellis, Manolis -- 5R24HD000836/HD/NICHD NIH HHS/ -- ES017166/ES/NIEHS NIH HHS/ -- F32 HL110473/HL/NHLBI NIH HHS/ -- F32HL110473/HL/NHLBI NIH HHS/ -- K99 HL119617/HL/NHLBI NIH HHS/ -- K99HL119617/HL/NHLBI NIH HHS/ -- P01 DA008227/DA/NIDA NIH HHS/ -- P30AG10161/AG/NIA NIH HHS/ -- P50 MH096890/MH/NIMH NIH HHS/ -- R01 AG015819/AG/NIA NIH HHS/ -- R01 AG017917/AG/NIA NIH HHS/ -- R01 ES024984/ES/NIEHS NIH HHS/ -- R01 ES024992/ES/NIEHS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG007175/HG/NHGRI NIH HHS/ -- R01 HG007354/HG/NHGRI NIH HHS/ -- R01AG15819/AG/NIA NIH HHS/ -- R01AG17917/AG/NIA NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- R01HG004037-S1/HG/NHGRI NIH HHS/ -- R01NS078839/NS/NINDS NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- RF1 AG015819/AG/NIA NIH HHS/ -- T32 ES007032/ES/NIEHS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- T32 GM081739/GM/NIGMS NIH HHS/ -- U01 ES017154/ES/NIEHS NIH HHS/ -- U01AG46152/AG/NIA NIH HHS/ -- U01DA025956/DA/NIDA NIH HHS/ -- U01ES017154/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U01ES017156/ES/NIEHS NIH HHS/ -- U01ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):317-30. doi: 10.1038/nature14248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Department of Computer Science, 300 Pasteur Dr., Lane Building, L301, Stanford, California 94305-5120, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Biological Chemistry, University of California, Los Angeles, 615 Charles E Young Dr South, Los Angeles, California 90095, USA. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Department of Stem Cell and Regenerative Biology, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA. ; Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Genomic Analysis Laboratory, Howard Hughes Medical Institute &The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA. ; 1] Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. [2] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA. ; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA. ; Department of Medicine, Division of Medical Genetics, University of Washington, 2211 Elliot Avenue, Seattle, Washington 98121, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Computer Science &Engineering, University of Connecticut, 371 Fairfield Way, Storrs, Connecticut 06269, USA. ; Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada. ; Bioinformatics Group, Department of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. ; Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. ; Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. ; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. ; 1] Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. [2] Department of Computer Science and Engineeering, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794-3600, USA. [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Molecular and Human Genetics Department, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. [3] Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA. ; Department of Biochemistry, Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, California 90089-9601, USA. ; ObGyn, Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, California 94143, USA. ; Center for Biomolecular Sciences and Engineering, University of Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. [3] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Department of Microbiology and Immunology, Diabetes Center, University of California, San Francisco, 513 Parnassus Ave, San Francisco, California 94143-0534, USA. ; 1] University of Wisconsin, Madison, Wisconsin 53715, USA. [2] Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53707, USA. ; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. [2] Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China. ; National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, USA. [3] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815-6789, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693563" target="_blank"〉PubMed〈/a〉

Beschreibung: Pancreatic beta cells lower insulin release in response to nutrient depletion. The question of whether starved beta cells induce macroautophagy, a predominant mechanism maintaining energy homeostasis, remains poorly explored. We found that, in contrast to many mammalian cells, macroautophagy in pancreatic beta cells was suppressed upon starvation. Instead, starved beta cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D (PKD), a key player in secretory granule biogenesis. Starvation-induced nascent granule degradation triggered lysosomal recruitment and activation of mechanistic target of rapamycin that suppressed macroautophagy. Switching from macroautophagy to insulin granule degradation was important to keep insulin secretion low upon fasting. Thus, beta cells use a PKD-dependent mechanism to adapt to nutrient availability and couple autophagy flux to secretory function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goginashvili, Alexander -- Zhang, Zhirong -- Erbs, Eric -- Spiegelhalter, Coralie -- Kessler, Pascal -- Mihlan, Michael -- Pasquier, Adrien -- Krupina, Ksenia -- Schieber, Nicole -- Cinque, Laura -- Morvan, Joelle -- Sumara, Izabela -- Schwab, Yannick -- Settembre, Carmine -- Ricci, Romeo -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):878-82. doi: 10.1126/science.aaa2628.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM, CNRS, Universite de Strasbourg, 67404 Illkirch, France. ; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. ; Dulbecco Telethon Institute and Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy. ; Dulbecco Telethon Institute and Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy. Medical Genetics, Department of Medical and Translational Science Unit, Federico II University, Via Pansini 5, 80131 Naples, Italy. ; Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM, CNRS, Universite de Strasbourg, 67404 Illkirch, France. Nouvel Hopital Civil, Laboratoire de Biochimie et de Biologie Moleculaire, Universite de Strasbourg, 67091 Strasbourg, France. romeo.ricci@igbmc.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700520" target="_blank"〉PubMed〈/a〉

Beschreibung: Pluripotency, the ability to generate any cell type of the body, is an evanescent attribute of embryonic cells. Transitory pluripotent cells can be captured at different time points during embryogenesis and maintained as embryonic stem cells or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both space and time, it seems counterintuitive that these two temporal states represent the full spectrum of organismal pluripotency. Here we show that by modulating culture parameters, a stem-cell type with unique spatial characteristics and distinct molecular and functional features, designated as region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained from mouse embryos and primate pluripotent stem cells, including humans. The ease of culturing and editing the genome of human rsPSCs offers advantages for regenerative medicine applications. The unique ability of human rsPSCs to generate post-implantation interspecies chimaeric embryos may facilitate our understanding of early human development and evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jun -- Okamura, Daiji -- Li, Mo -- Suzuki, Keiichiro -- Luo, Chongyuan -- Ma, Li -- He, Yupeng -- Li, Zhongwei -- Benner, Chris -- Tamura, Isao -- Krause, Marie N -- Nery, Joseph R -- Du, Tingting -- Zhang, Zhuzhu -- Hishida, Tomoaki -- Takahashi, Yuta -- Aizawa, Emi -- Kim, Na Young -- Lajara, Jeronimo -- Guillen, Pedro -- Campistol, Josep M -- Esteban, Concepcion Rodriguez -- Ross, Pablo J -- Saghatelian, Alan -- Ren, Bing -- Ecker, Joseph R -- Izpisua Belmonte, Juan Carlos -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 May 21;521(7552):316-21. doi: 10.1038/nature14413. Epub 2015 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA. ; 1] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Integrated Genomics, La Jolla, California 92037, USA. ; Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA. ; 1] The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA [2] Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan. ; Grado en Medicina, Universidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe 30107, Spain. ; 1] Grado en Medicina, Universidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe 30107, Spain [2] Fundacion Pedro Guillen, Clinica Cemtro, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain. ; Hospital Clinic of Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain. ; University of California, Davis, Davis, California 95616, USA. ; The Salk Institute for Biological Studies, Peptide Biology Laboratory, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25945737" target="_blank"〉PubMed〈/a〉