Abstract:
:A human pancreatic beta-cell line that is functionally equivalent to primary beta-cells has not been available. We established a reversibly immortalized human beta-cell clone (NAKT-15) by transfection of primary human beta-cells with a retroviral vector containing simian virus 40 large T-antigen (SV40T) and human telomerase reverse transcriptase (hTERT) cDNAs flanked by paired loxP recombination targets, which allow deletion of SV40T and TERT by Cre recombinase. Reverted NAKT-15 cells expressed beta-cell transcription factors (Isl-1, Pax 6, Nkx 6.1, Pdx-1), prohormone convertases 1/3 and 2, and secretory granule proteins, and secreted insulin in response to glucose, similar to normal human islets. Transplantation of NAKT-15 cells into streptozotocin-induced diabetic severe combined immunodeficiency mice resulted in perfect control of blood glucose within 2 weeks; mice remained normoglycemic for longer than 30 weeks. The establishment of this cell line is one step toward a potential cure of diabetes by transplantation.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Narushima M,Kobayashi N,Okitsu T,Tanaka Y,Li SA,Chen Y,Miki A,Tanaka K,Nakaji S,Takei K,Gutierrez AS,Rivas-Carrillo JD,Navarro-Alvarez N,Jun HS,Westerman KA,Noguchi H,Lakey JR,Leboulch P,Tanaka N,Yoon JWdoi
10.1038/nbt1145subject
Has Abstractpub_date
2005-10-01 00:00:00pages
1274-82issue
10eissn
1087-0156issn
1546-1696pii
nbt1145journal_volume
23pub_type
杂志文章abstract::Centromeric variation has been linked to cancer and infertility, but centromere sequences contain multiple tandem repeats and can only be assembled manually from long error-prone reads. Here we describe the centroFlye algorithm for centromere assembly using long error-prone reads, and apply it to assemble human centro...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0582-4
更新日期:2020-11-01 00:00:00
abstract::Transgenic crops are approved for release in some countries, while many more countries are wrestling with the issue of how to conduct risk assessments. Controls on field trials often include monitoring of horizontal gene transfer (HGT) from crops to surrounding soil microorganisms. Our analysis of antibiotic-resistant...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1009
更新日期:2004-09-01 00:00:00
abstract::Paralleling the diversity of genetic and protein activities, pathologic human tissues also exhibit diverse radiographic features. Here we show that dynamic imaging traits in non-invasive computed tomography (CT) systematically correlate with the global gene expression programs of primary human liver cancer. Combinatio...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1306
更新日期:2007-06-01 00:00:00
abstract::Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventio...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1073
更新日期:2005-03-01 00:00:00
abstract::We describe a novel approach to design a set of primers selective for large groups of genes. This method is based on the distribution frequency of all nucleotide combinations (octa- to decanucleotides), and the combined ability of primer pairs, based on these oligonucleotides, to detect genes. By analyzing 1000 human ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0796-857
更新日期:1996-07-01 00:00:00
abstract::Genome editing with targeted nucleases and DNA donor templates homologous to the break site has proven challenging in human hematopoietic stem and progenitor cells (HSPCs), and particularly in the most primitive, long-term repopulating cell population. Here we report that combining electroporation of zinc finger nucle...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3408
更新日期:2015-12-01 00:00:00
abstract::The interaction between the HSP90 chaperone and its client kinases is sensitive to the conformational status of the kinase, and stabilization of the kinase fold by small molecules strongly decreases chaperone interaction. Here we exploit this observation and assay small-molecule binding to kinases in living cells, usi...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2620
更新日期:2013-07-01 00:00:00
abstract::Numerous biological processes involve the recognition of a specific pattern of binding sites on a target protein or surface. Although ligands displayed by disordered scaffolds form stochastic rather than specific patterns, theoretical models predict that recognition will occur between patterns that are characterized b...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1204
更新日期:2006-05-01 00:00:00
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journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt990
更新日期:2004-08-01 00:00:00
abstract::The vast selection of Drosophila mutants is an extraordinary resource for exploring molecular events underlying development and disease. We have designed and constructed an instrument that automatically separates Drosophila embryos of one genotype from a larger population of embryos, based on a fluorescent protein mar...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/84422
更新日期:2001-02-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature biotechnology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41587-020-0427-1
更新日期:2020-03-01 00:00:00
abstract::Tocotrienols are the primary form of vitamin E in seeds of most monocot plants, including cereals such as rice and wheat. As potent antioxidants, tocotrienols contribute to the nutritive value of cereal grains in human and livestock diets. cDNAs encoding homogentisic acid geranylgeranyl transferase (HGGT), which catal...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt853
更新日期:2003-09-01 00:00:00
abstract::The functional state of a cell is largely determined by the spatiotemporal organization of its proteome. Technologies exist for measuring particular aspects of protein turnover and localization, but comprehensive analysis of protein dynamics across different scales is possible only by combining several methods. Here w...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2281
更新日期:2012-06-24 00:00:00
abstract::Although mass spectrometry is well suited to identifying thousands of potential protein post-translational modifications (PTMs), it has historically been biased towards just a few. To measure the entire set of PTMs across diverse proteomes, software must overcome the dual challenges of covering enormous search spaces ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0067-5
更新日期:2019-04-01 00:00:00
abstract::The discovery of large multiprotein complexes in cells has increased the demand for improved heterologous protein production techniques to study their molecular structure and function. Here we describe MultiBac, a simple and versatile system for generating recombinant baculovirus DNA to express protein complexes compr...
journal_title:Nature biotechnology
pub_type: 信件
doi:10.1038/nbt1036
更新日期:2004-12-01 00:00:00
abstract::In the version of this article initially published, Lena Dolman's second affiliation was given as Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. The correct second affiliation is Ontario Institute for Cancer Research, Toronto, Ontario, Canada. The error has been corrected in the HTML ...
journal_title:Nature biotechnology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41587-019-0094-2
更新日期:2019-04-01 00:00:00
abstract::We present 1,003 reference genomes that were sequenced as part of the Genomic Encyclopedia of Bacteria and Archaea (GEBA) initiative, selected to maximize sequence coverage of phylogenetic space. These genomes double the number of existing type strains and expand their overall phylogenetic diversity by 25%. Comparativ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3886
更新日期:2017-07-01 00:00:00
abstract::Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-Methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in euka...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.2398
更新日期:2012-11-01 00:00:00
abstract::The potential therapeutic applications of encapsulated cells are enormous. In the US alone, it has been estimated that nearly half-a-trillion dollars are spent each year to care for patients who suffer tissue loss or dysfunction. Over 6 million patients suffer from neurodegenerative disorders such as Alzheimer's disea...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0996-1107
更新日期:1996-09-01 00:00:00
abstract::Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we presen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3350
更新日期:2015-10-01 00:00:00
abstract::Recent studies have demonstrated the important enzymatic, structural and regulatory roles of RNA in the cell. Here we present a post-transcriptional regulation system in Escherichia coli that uses RNA to both silence and activate gene expression. We inserted a complementary cis sequence directly upstream of the riboso...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt986
更新日期:2004-07-01 00:00:00
abstract::Academic researchers have regularly ignored patents on key technologies as a strategy to maneuver around patent thickets and freedom-to-operate issues, but they may be more at risk than they realize. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1107-1225
更新日期:2007-11-01 00:00:00
abstract::Nitrogen-use efficiency of indica varieties of rice is superior to that of japonica varieties. We apply 16S ribosomal RNA gene profiling to characterize root microbiota of 68 indica and 27 japonica varieties grown in the field. We find that indica and japonica recruit distinct root microbiota. Notably, indica-enriched...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0104-4
更新日期:2019-06-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
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pub_type: 已发布勘误
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更新日期:2019-11-01 00:00:00
abstract::Type I polyketide synthase (PKS) genes consist of modules approximately 3-6 kb long, which encode the structures of 2-carbon units in polyketide products. Alteration or replacement of individual PKS modules can lead to the biosynthesis of 'unnatural' natural products but existing techniques for this are time consuming...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1128
更新日期:2005-09-01 00:00:00
abstract::Artificial transcription factors containing designer zinc-finger DNA-binding domains (DBDs) have been used to activate or repress expression of a growing number of endogenous genes. We have combined targeted zinc-finger DBD technology with a dimerizer-regulated gene expression system to permit the small-molecule contr...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0702-729
更新日期:2002-07-01 00:00:00
abstract::Analyzing patent data from 1995-2005 show the increasing importance of patenting by small and medium-sized biotech companies. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0606-643
更新日期:2006-06-01 00:00:00
abstract::Reengineering the receptor footprints of adeno-associated virus (AAV) isolates may yield variants with improved properties for clinical applications. We generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence in a previously identified heparan sulfate receptor footprint with corresponding resid...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1599
更新日期:2010-01-01 00:00:00
abstract::RNA-interference (RNAi) is a potent mechanism, conserved from plants to humans for specific silencing of genes, which holds promise for functional genomics and gene-targeted therapies. Here we show that bacteria engineered to produce a short hairpin RNA (shRNA) targeting a mammalian gene induce trans-kingdom RNAi in v...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1211
更新日期:2006-06-01 00:00:00
abstract::RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the pros...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3412
更新日期:2015-12-01 00:00:00