Abstract:
:CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated Kras(G12D) mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.
journal_name
Celljournal_title
Cellauthors
Platt RJ,Chen S,Zhou Y,Yim MJ,Swiech L,Kempton HR,Dahlman JE,Parnas O,Eisenhaure TM,Jovanovic M,Graham DB,Jhunjhunwala S,Heidenreich M,Xavier RJ,Langer R,Anderson DG,Hacohen N,Regev A,Feng G,Sharp PA,Zhang Fdoi
10.1016/j.cell.2014.09.014subject
Has Abstractpub_date
2014-10-09 00:00:00pages
440-55issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(14)01163-5journal_volume
159pub_type
杂志文章相关文献
CELL文献大全abstract::Viral infection causes the host to activate an antiviral response that, in part, is dependent on mitochondrial antiviral signaling protein (MAVS) to stimulate type I interferons. Zhang et al. (2019) demonstrate that glucose-generated lactate interacts with MAVS to suppress type I interferons. This study links glucose ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2019.05.057
更新日期:2019-06-27 00:00:00
abstract::The crystal structure of the snake toxin fasciculin, bound to mouse acetylcholinesterase (mAChE), at 3.2 A resolution reveals a synergistic three-point anchorage consistent with the picomolar dissociation constant of the complex. Loop II of fasciculin contains a cluster of hydrophobic residues that interact with the p...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90128-0
更新日期:1995-11-03 00:00:00
abstract::The extracellular space (ECS) of the brain has an extremely complex spatial organization, which has defied conventional light microscopy. Consequently, despite a marked interest in the physiological roles of brain ECS, its structure and dynamics remain largely inaccessible for experimenters. We combined 3D-STED micros...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2018.02.007
更新日期:2018-02-22 00:00:00
abstract::Sixty-one codons specify 20 amino acids, offering cells many options for encoding a polypeptide sequence. Two new studies (Cannarrozzi et al., 2010; Tuller et al., 2010) now foster the idea that patterns of codon usage can control ribosome speed, fine-tuning translation to increase the efficiency of protein synthesis....
journal_title:Cell
pub_type: 评论,杂志文章,评审
doi:10.1016/j.cell.2010.03.033
更新日期:2010-04-16 00:00:00
abstract::We have devised a genetic strategy to isolate the target of acidic activation domains of transcriptional activators based on toxicity in yeast cells of the chimeric activator, GAL4-VP16. Toxicity required the integrity of both the VP16 acidic activation domain and the GAL4 DNA-binding domain, suggesting that inhibitio...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90100-q
更新日期:1992-07-24 00:00:00
abstract::Fluorescent proteins are commonly used to label cells across organisms, but the unmodified forms cannot control biological activities. Using GFP-binding proteins derived from Camelid antibodies, we co-opted GFP as a scaffold for inducing formation of biologically active complexes, developing a library of hybrid transc...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2013.07.021
更新日期:2013-08-15 00:00:00
abstract::Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.03.049
更新日期:2014-04-24 00:00:00
abstract::To relate different forms of synaptic plasticity to the formation and maintenance of place cells in the hippocampus, we have recorded place cells in freely behaving, transgenic mice that express a mutated Ca2+-independent form of CaM Kinase II. These mice have normal long-term potentiation (LTP) at 100 Hz, but they la...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81829-2
更新日期:1996-12-27 00:00:00
abstract::The structure and organization on the Escherichia coli chromosome of the gene cluster coding for two methionine tRNAs (tRNAmMet), four glutamine tRNAs (two tRNA1Gln and two tRNA2Gln), and a previously unidentified tRNA (called tRNAx) have been studied by restriction enzyme analysis and DNA sequencing, utilizing a spec...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90288-9
更新日期:1981-01-01 00:00:00
abstract::While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we i...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2018.06.039
更新日期:2018-07-26 00:00:00
abstract::ABCA1, an ATP-binding cassette (ABC) subfamily A exporter, mediates the cellular efflux of phospholipids and cholesterol to the extracellular acceptor apolipoprotein A-I (apoA-I) for generation of nascent high-density lipoprotein (HDL). Mutations of human ABCA1 are associated with Tangier disease and familial HDL defi...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.05.020
更新日期:2017-06-15 00:00:00
abstract::Muscle fibers specialized for fast or slow contraction are arrayed in characteristic patterns within developing limbs. Clones of myoblasts analyzed in vitro express fast and slow myosin isoforms typical of the muscle from which they derive. As a result, it has been suggested that distinct myoblast lineages generate an...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90142-y
更新日期:1992-02-21 00:00:00
abstract::The Drosophila transforming growth factor beta (TGF-beta) homolog Decapentaplegic (Dpp) acts as a morphogen that forms a long-range concentration gradient to direct the anteroposterior patterning of the wing. Both planar transcytosis initiated by Dynamin-mediated endocytosis and extracellular diffusion have been propo...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2004.09.031
更新日期:2004-10-15 00:00:00
abstract::Although specific microRNAs (miRNAs) can be upregulated in cancer, global miRNA downregulation is a common trait of human malignancies. The mechanisms of this phenomenon and the advantages it affords remain poorly understood. Here we identify a microRNA family, miR-103/107, that attenuates miRNA biosynthesis by target...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2010.05.017
更新日期:2010-06-25 00:00:00
abstract::Recent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2, other B cell components are required for lymphoid-restricted, octamer site-mediated immunoglobulin gene promoter activity. Using a genetic screen in yeast, we have isolated B cell-derived cDNAs encoding Oc...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90500-6
更新日期:1995-02-10 00:00:00
abstract::Three different cases of pancreatic beta cell hyperplasia in mice are accompanied by an increase in a subclass of cells expressing tyrosine hydroxylase (TH), a neuronal enzyme. In the nontumorigenic cases of islet growth during normal pregnancy and in the obese mutant mouse, the TH-insulin cells do not divide, in cont...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90534-x
更新日期:1988-01-15 00:00:00
abstract::Using positional cloning strategies, we have identified a CTG triplet repeat that undergoes expansion in myotonic dystrophy patients. This sequence is highly variable in the normal population. PCR analysis of the interval containing this repeat indicates that unaffected individuals have been 5 and 27 copies. Myotonic ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90154-5
更新日期:1992-02-21 00:00:00
abstract::Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent up...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2012.03.042
更新日期:2012-05-25 00:00:00
abstract::Brassinosteroids (BRs) signal through a plasma membrane-localized receptor kinase to regulate plant growth and development. We showed previously that a novel protein, BES1, accumulates in the nucleus in response to BRs, where it plays a role in BR-regulated gene expression; however, the mechanism by which BES1 regulat...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2004.11.044
更新日期:2005-01-28 00:00:00
abstract::The initiation of transcription from the nitrogen-regulated promoter glnAp2 requires RNA polymerase containing sigma 54, the transcriptional activator NRI, and the protein kinase NRII, responsible for the conversion of NRI to the active NRI-phosphate. NRI-phosphate does not increase the ability of sigma 54-containing ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(87)90170-x
更新日期:1987-09-25 00:00:00
abstract::Two allelic forms of the natural chicken ovalbumin gene have been independently cloned. These alleles differ from each other by an Eco RI restriction cleavage site in one of the seven intervening sequences within the natural ovalbumin gene. Restriction endonuclease mapping and sequence analyses of these cloned genotyp...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90201-0
更新日期:1979-01-01 00:00:00
abstract::The redox-regulated chaperone Hsp33 protects organisms against oxidative stress that leads to protein unfolding. Activation of Hsp33 is triggered by the oxidative unfolding of its own redox-sensor domain, making Hsp33 a member of a recently discovered class of chaperones that require partial unfolding for full chapero...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2012.01.045
更新日期:2012-03-02 00:00:00
abstract::Cell lines stably transfected with metal inducible, MT-fos chimeric genes were used to study the ability of the c-fos gene product, Fos, to act as a transcriptional trans-activator. In 3T3MTfos cells, induction of Fos expression led to specific trans-activation of an AP-1 responsive reporter gene. Induction of Fos exp...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90076-1
更新日期:1988-08-12 00:00:00
abstract::Ventral midline cells at different rostrocaudal levels of the central nervous system exhibit distinct properties but share the ability to pattern the dorsoventral axis of the neural tube. We show here that ventral midline cells acquire distinct identities in response to the different signaling activities of underlying...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80334-7
更新日期:1997-07-25 00:00:00
abstract::Escherichia coli and Micrococcus luteus DNA topoisomerase I are found to promote catenation of double-stranded DNA rings. At low DNA concentration dimeric catenanes are the major catenated products; at high DNA concentration or when spermidine is present, catenanes containing more than two rings are formed. There is n...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90174-9
更新日期:1980-11-01 00:00:00
abstract::Senescence in Podospora anserina has long been shown to be under cytoplasmic control. Comparison of DNAs isolated from young and senescent cultures made it possible to detect the presence, in senescent cultures only, of a specific DNA (SEN-DNA). This DNA consists of repeated sequences arranged in a multimeric set of c...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(80)90126-9
更新日期:1980-08-01 00:00:00
abstract::The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on t...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81050-8
更新日期:1996-03-08 00:00:00
abstract::Subsets of long-lived, tumor-initiating stem cells often escape cancer therapies. However, sources and mechanisms that generate tumor heterogeneity and drug-resistant cell population are still unfolding. Here, we devise a functional reporter system to lineage trace and/or genetic ablate signaling in TGF-β-activated sq...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2015.01.043
更新日期:2015-02-26 00:00:00
abstract::The emergence of SARS-CoV-2 has driven a global research effort to identify medical countermeasures at an unprecedented pace. In this issue of Cell, Cao et al. identify thousands of SARS-CoV-2 neutralizing antibodies from convalescent donors. The authors improve our understanding of immunity against the coronavirus sp...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2020.06.017
更新日期:2020-07-09 00:00:00
abstract::A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein. Southern blotting with PrP cDNA revealed a single gene with the same restriction patterns in...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(85)90333-2
更新日期:1985-04-01 00:00:00