Abstract:
:In vivo genome editing represents a powerful strategy for both understanding basic biology and treating inherited diseases. However, it remains a challenge to develop universal and efficient in vivo genome-editing tools for tissues that comprise diverse cell types in either a dividing or non-dividing state. Here, we describe a versatile in vivo gene knock-in methodology that enables the targeting of a broad range of mutations and cell types through the insertion of a minigene at an intron of the target gene locus using an intracellularly linearized single homology arm donor. As a proof-of-concept, we focused on a mouse model of premature-aging caused by a dominant point mutation, which is difficult to repair using existing in vivo genome-editing tools. Systemic treatment using our new method ameliorated aging-associated phenotypes and extended animal lifespan, thus highlighting the potential of this methodology for a broad range of in vivo genome-editing applications.
journal_name
Cell Resjournal_title
Cell researchauthors
Suzuki K,Yamamoto M,Hernandez-Benitez R,Li Z,Wei C,Soligalla RD,Aizawa E,Hatanaka F,Kurita M,Reddy P,Ocampo A,Hishida T,Sakurai M,Nemeth AN,Nuñez Delicado E,Campistol JM,Magistretti P,Guillen P,Rodriguez Esteban C,Gdoi
10.1038/s41422-019-0213-0subject
Has Abstractpub_date
2019-10-01 00:00:00pages
804-819issue
10eissn
1001-0602issn
1748-7838pii
10.1038/s41422-019-0213-0journal_volume
29pub_type
杂志文章相关文献
CELL RESEARCH文献大全abstract::Entry into mitosis is driven by signaling cascades of mitotic kinases. Our recent studies show that TTK, a kinetochore-associated protein kinase, interacts with CENP-E, a mitotic kinesin located to corona fiber of kinetochore. Using immunoelectron microscopy, here we show that TTK is present at the nuclear pore adjace...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7290186
更新日期:2003-12-01 00:00:00
abstract::The nuclear pore complex (NPC) exhibits structural plasticity and has only been characterized at local resolutions of up to 15 Å for the cytoplasmic ring (CR). Here we present a single-particle cryo-electron microscopy (cryo-EM) structure of the CR from Xenopus laevis NPC at average resolutions of 5.5-7.9 Å, with loca...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/s41422-020-0319-4
更新日期:2020-06-01 00:00:00
abstract::Plant responses to developmental and environmental cues are often mediated by calcium (Ca(2+)) signals that are transmitted by diverse calcium sensors. The calcineurin B-like (CBL) protein family represents calcium sensors that decode calcium signals through specific interactions with a group of CBL-interacting protei...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2012.161
更新日期:2012-12-01 00:00:00
abstract::Mitogen-activated protein kinase (MAPK) cascades play important roles in regulating plant innate immune responses. In a genetic screen to search for mutants with constitutive defense responses, we identified multiple alleles of mpk4 and mekk1 that exhibit cell death and constitutive defense responses. Bimolecular fluo...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2008.300
更新日期:2008-12-01 00:00:00
abstract::The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2008.16
更新日期:2008-02-01 00:00:00
abstract::A paracrine regulation was recently proposed in human embryonic stem cells (hESCs) grown in mouse embryonic fibroblast (MEF)-conditioned media (MEF-CM), where hESCs spontaneously differentiate into autologous fibroblast-like cells to maintain culture homeostasis by producing TGF-beta and insulin-like growth factor-II ...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2009.35
更新日期:2009-06-01 00:00:00
abstract::The tumor suppressor PTEN controls a variety of biological processes including cell proliferation, growth, migration, and death. As a master cellular regulator, PTEN itself is also subjected to deliberated regulation to ensure its proper function. Defects in PTEN regulation have a profound impact on carcinogenesis. In...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2008.83
更新日期:2008-08-01 00:00:00
abstract::The pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) belongs to the secretin receptor family and is widely distributed in the central neural system and peripheral organs. Abnormal activation of the receptor mediates trigeminovascular activation and sensitization, which is highly related to mi...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/s41422-020-0280-2
更新日期:2020-05-01 00:00:00
abstract::DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addition, they are commonly generated during V(D)J recombination, an essential aspect of the developing immune system. Failure to effectively repair these DSBs can result in chromosome breakage, cell death, on...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2008.3
更新日期:2008-01-01 00:00:00
abstract::Fishes, the biggest and most diverse community in vertebrates are good experimental models for studies of cell and developmental biology by many favorable characteristics. Nuclear transplantation in fish has been thoroughly studied in China since 1960s. Fish nuclei of embryonic cells from different genera were transpl...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/sj.cr.7290032
更新日期:2000-03-01 00:00:00
abstract::Vascular integrity helps maintain brain microenvironment homeostasis, which is critical for the normal development and function of the central nervous system. It is known that neural cells can regulate brain vascular integrity. However, due to the high complexity of neurovascular interactions involved, understanding o...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2017.62
更新日期:2017-07-01 00:00:00
abstract::Intracellular redox homeostasis plays a critical role in determining tumor cells' sensitivity to drug-induced apoptosis. Here we investigated the role of thioredoxin-1 (TRX1), a key component of redox regulation, in arsenic trioxide (As(2)O(3))-induced apoptosis. Over-expression of wild-type TRX1 in HepG(2) cells led ...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2007.112
更新日期:2008-04-01 00:00:00
abstract::Mitochondria have long been considered to be the powerhouse of the living cell, generating energy in the form of the molecule ATP via the process of oxidative phosphorylation. In the past 20 years, it has been recognised that they also play an important role in the implementation of apoptosis, or programmed cell death...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/sj.cr.7290267
更新日期:2005-01-01 00:00:00
abstract::Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified protein C receptor (Procr) as a surface marker on mammary stem cells (MaSCs) locate...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/s41422-019-0225-9
更新日期:2019-10-01 00:00:00
abstract::Human gastric cancer MKN-45 cells were transfected with pULB 3238, a plasmid carrying MVMp NS-1 gene with its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR. After the integration and expression of NS-1 gene, some of the transfectants died, while others remained alive, but the growth f...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.1997.22
更新日期:1997-12-01 00:00:00
abstract::During meiotic cell division, proper chromosome synapsis and accurate repair of DNA double strand breaks (DSBs) are required to maintain genomic integrity, loss of which leads to apoptosis or meiotic defects. The mechanisms underlying meiotic chromosome synapsis, DSB repair and apoptosis are not fully understood. Here...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2012.2
更新日期:2012-05-01 00:00:00
abstract::Two distinct nuclear factor κB (NFκB) signaling pathways have been described; the canonical pathway that mediates inflammatory responses, and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis. The former is dependent on the IκB kinase adaptor ...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2010.161
更新日期:2011-01-01 00:00:00
abstract::CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcriptional regulatory factor that inhibits cell proliferation, and alternative translational initiation produces two polypeptides, C/EBPalphap30 and C/EBPalphap42. By expression profiling, it was revealed that C/EBPalphap30 specifically inhibited a unique set...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7310121
更新日期:2007-04-01 00:00:00
abstract::Implantation involves complex signaling networks, which direct morphological and molecular transformation of the embryo and the uterus and establish the trajectory of normal pregnancy. The recent work by Zhang et al. published in Cell Research, identifies the transcriptional regulator, Rbpj, as essential for uterine c...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2014.110
更新日期:2014-09-01 00:00:00
abstract::Since its discovery in 1989, researchers strive after a small animal model for Hepatitis C virus infection, so far with very limited success. A study recently published in Nature now for the first time reports the recapitulation of the complete life cycle of this virus in inbred mice with a functional adaptive immune ...
journal_title:Cell research
pub_type: 评论,杂志文章
doi:10.1038/cr.2013.132
更新日期:2013-12-01 00:00:00
abstract::Our previous study showed that hydroxyurea (Hu) could induce HEL cells to express human beta-globin gene. However the molecular mechanisms by which the expression of beta-globin gene is activated and regulated are poorly understood. Here we show that the binding patterns between the core DNA sequences (HS2 core sequen...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7290144
更新日期:2002-12-01 00:00:00
abstract::Differentiation of inflammatory macrophages from monocytes is characterized by an orderly integration of epigenetic and transcriptional regulatory mechanisms guided by lineage-determining transcription factors such as PU.1. Further activation of macrophages leads to a stimulus- or microenvironment-specific signal inte...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2016.1
更新日期:2016-02-01 00:00:00
abstract::We have developed a cell-free system that can trigger the nuclei purified from mouse liver and suspension-cultured carrot cells to undergo apoptosis as defined by the formation of apoptotic bodies and nucleosomal DNA fragments. The effects of different divalent cations and cycloheximide on DNA cleavage in this system ...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7290008
更新日期:1999-06-01 00:00:00
abstract::A monoclonal antibody, LC-1, recognizing lung cancer associated common antigens was obtained in authors' laboratory. Its single chain Fv fragment (ScFv) named LC-1 ScFv was constructed based on recombinant phage displayed techniques. For expression on cell membrane, LC-1 ScFv was cloned into pDisplay vector, which dir...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7290109
更新日期:2002-03-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 kDa gelatinase A/type IV collagenase (MMP-2), and 92 kDa gelatinase B/type IV collagenase (MMP-9) diss...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.1998.17
更新日期:1998-09-01 00:00:00
abstract::High-density lipoproteins (HDLs) have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their ben...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/sj.cr.7310097
更新日期:2006-10-01 00:00:00
abstract::Heterotrimeric G proteins are known to function as messengers in numerous signal transduction pathways. The null mutation of RGA (rice heterotrimeric G protein alpha subunit), which encodes the alpha subunit of heterotrimeric G protein in rice, causes severe dwarfism and reduced responsiveness to gibberellic acid in r...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/sj.cr.7310111
更新日期:2006-12-01 00:00:00
abstract::Craniofacial anomalies (CFAs) characterized by birth defects of skull and facial bones are the most frequent congenital disease. Genomic analysis has identified multiple genes responsible for CFAs; however, the underlying genetic mechanisms for the majority of CFAs remain largely unclear. Our previous study revealed t...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.2016.51
更新日期:2016-06-01 00:00:00
abstract::In order to analyze the mechanism of immuno-modulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay, checked the changes of mRNA expression pattern of several cytokine genes during the immuno-modulation. It has been found that, after treating peritoneal suppressor macrophag...
journal_title:Cell research
pub_type: 杂志文章
doi:10.1038/cr.1998.32
更新日期:1998-12-01 00:00:00
abstract::Ruptured and intact plasma membranes are classically considered as hallmarks of necrotic and apoptotic cell death, respectively. As such, apoptosis is usually considered a non-inflammatory process while necrosis triggers inflammation. Recent studies on necroptosis and pyroptosis, two types of programmed necrosis, reve...
journal_title:Cell research
pub_type: 杂志文章,评审
doi:10.1038/cr.2017.133
更新日期:2018-01-01 00:00:00