Abstract:
:The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue's magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Ku T,Swaney J,Park JY,Albanese A,Murray E,Cho JH,Park YG,Mangena V,Chen J,Chung Kdoi
10.1038/nbt.3641subject
Has Abstractpub_date
2016-09-01 00:00:00pages
973-81issue
9eissn
1087-0156issn
1546-1696pii
nbt.3641journal_volume
34pub_type
杂志文章abstract::Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of plac...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4297
更新日期:2018-11-19 00:00:00
abstract::An analysis of US Federal Circuit decisions shows strategies for designing around patents. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0508-519
更新日期:2008-05-01 00:00:00
abstract::Understanding how proteins and their complex interaction networks convert the genomic information into a dynamic living organism is a fundamental challenge in biological sciences. As an important step towards understanding the systems biology of a complex eukaryote, we cataloged 63% of the predicted Drosophila melanog...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1300
更新日期:2007-05-01 00:00:00
abstract::Human embryonic stem cells (hESCs) have two properties of interest for the development of cell therapies: self-renewal and the potential to differentiate into all major lineages of somatic cells in the human body. Widespread clinical application of hESC-derived cells will require culture methods that are low-cost, rob...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1629
更新日期:2010-06-01 00:00:00
abstract::The green fluorescent protein (GFP) from the jellyfish Aequorea victoria and its fluorescent homologs from Anthozoa corals have become invaluable tools for in vivo imaging of cells and tissues. Despite spectral and chromophore diversity, about 100 cloned members of the GFP-like protein family possess common structural...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt943
更新日期:2004-03-01 00:00:00
abstract::Epigenetic mechanisms integrate genetic and environmental causes of disease, but comprehensive genome-wide analyses of epigenetic modifications have not yet demonstrated robust association with common diseases. Using Illumina HumanMethylation450 arrays on 354 anti-citrullinated protein antibody-associated rheumatoid a...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2487
更新日期:2013-02-01 00:00:00
abstract::We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3353
更新日期:2015-10-01 00:00:00
abstract::Biological systems are controlled by protein complexes that associate into dynamic protein interaction networks. We describe a strategy that analyzes protein complexes through the integration of label-free, quantitative mass spectrometry and computational analysis. By evaluating peptide intensity profiles throughout t...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1289
更新日期:2007-03-01 00:00:00
abstract::DNA charge transport chemistry is found to provide a sensitive method for probing protein-dependent changes in DNA structure and enzymatic reactions. Here we describe the development of an electrochemical assay of protein binding to DNA-modified electrodes based upon the detection of associated perturbations in DNA ba...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0302-282
更新日期:2002-03-01 00:00:00
abstract::After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base seq...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.3765
更新日期:2017-03-01 00:00:00
abstract::A broad-specificity delta 9 desaturase gene was cloned from the cyanobacterium Anacystis nidulans. The enzyme introduces a cis-double bond at the delta 9 position of both 16 and 18 carbon saturated fatty acids linked to many kinds of membrane lipids. The gene was stably introduced into tobacco plants under transcripti...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0896-1003
更新日期:1996-08-01 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
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::Selectable marker genes are required to ensure the efficient genetic modification of crops. Economic incentives and safety concerns have prompted the development of several strategies (site-specific recombination, homologous recombination, transposition, and co-transformation) to eliminate these genes from the genome ...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0602-575
更新日期:2002-06-01 00:00:00
abstract::Can new approaches for deriving human stem cells circumnavigate existing patents that dominate embryonic stem cell intellectual property? ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0406-411
更新日期:2006-04-01 00:00:00
abstract::A major challenge for fluorescence imaging of living mammalian cells is maintaining viability following prolonged exposure to excitation illumination. We have monitored the dynamics of mitochondrial distribution in hamster embryos at frequent intervals over 24 h using two-photon microscopy (1,047 nm) while maintaining...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/11698
更新日期:1999-08-01 00:00:00
abstract::Rice is a staple crop that has undergone substantial phenotypic and physiological changes during domestication. Here we resequenced the genomes of 40 cultivated accessions selected from the major groups of rice and 10 accessions of their wild progenitors (Oryza rufipogon and Oryza nivara) to >15 × raw data coverage. W...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2050
更新日期:2011-12-11 00:00:00
abstract::Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, nei...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3585
更新日期:2016-08-01 00:00:00
abstract::Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2519
更新日期:2013-04-01 00:00:00
abstract::New high-dimensional, single-cell technologies offer unprecedented resolution in the analysis of heterogeneous tissues. However, because these technologies can measure dozens of parameters simultaneously in individual cells, data interpretation can be challenging. Here we present viSNE, a tool that allows one to map h...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2594
更新日期:2013-06-01 00:00:00
abstract::Lactobacillus sakei is a psychotrophic lactic acid bacterium found naturally on fresh meat and fish. This microorganism is widely used in the manufacture of fermented meats and has biotechnological potential in biopreservation and food safety. We have explored the 1,884,661-base-pair (bp) circular chromosome of strain...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1160
更新日期:2005-12-01 00:00:00
abstract::We have developed a generic procedure to purify proteins expressed at their natural level under native conditions using a novel tandem affinity purification (TAP) tag. The TAP tag allows the rapid purification of complexes from a relatively small number of cells without prior knowledge of the complex composition, acti...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/13732
更新日期:1999-10-01 00:00:00
abstract::The excitement and controversy surrounding the potential role of human embryonic stem (ES) cells in transplantation therapy have often overshadowed their potentially more important use as a basic research tool for understanding the development and function of human tissues. Human ES cells can proliferate without a kno...
journal_title:Nature biotechnology
pub_type:
doi:10.1038/nbt761
更新日期:2002-12-01 00:00:00
abstract::Epigenetic modifications constitute a complex regulatory layer on top of the genome sequence. Pluripotent and differentiated cells provide a powerful system for investigating how the epigenetic code influences cellular fate. High-throughput sequencing of these cell types has yielded DNA methylation maps at single-nucl...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.1684
更新日期:2010-10-01 00:00:00
abstract::Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolog of the central regulator of peroxide stress response in enteric bacteria. Inactivation of oxyR is specific for M. tuberculosis and other members of the M. tuberculosis complex. This phenomenon appears as a paradox due to the ability of this organi...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1196-1557
更新日期:1996-11-01 00:00:00
abstract::In the version of this article initially published, Betalutin was described as directing a radioisotope to CD45-expressing B cells; in fact, it directs it to CD37-expressing B cells. The error has been corrected in the HTML and PDF versions of the article. ...
journal_title:Nature biotechnology
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41587-019-0030-5
更新日期:2019-02-01 00:00:00
abstract::Phosphorus (P) is one of the most important nutrients limiting agricultural production worldwide. In acid and alkaline soils, which make up over 70% of the world's arable land, P forms insoluble compounds that are not available for plant use. To reduce P deficiencies and ensure plant productivity, nearly 30 million to...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/74531
更新日期:2000-04-01 00:00:00
abstract::Thermostable enzymes combine catalytic specificity with the toughness required to withstand industrial reaction conditions. Stabilized enzymes also provide robust starting points for evolutionary improvement of other protein properties. We recently created a library of at least 2,300 new active chimeras of the biotech...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1333
更新日期:2007-09-01 00:00:00
abstract::Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed compr...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2890
更新日期:2014-05-01 00:00:00
abstract::High-density short oligonucleotide microarrays have become a widely used tool for measuring gene expression on a large scale. However, details of the mechanism of binding on microarrays remain unclear. Short oligonucleotide probes currently synthesized on microarrays are often ineffective as a result of limited sequen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt836
更新日期:2003-07-01 00:00:00